Ophthalmia Neonatorum

Etiology

Research has identified various microorganisms as the causative agents of this eye disease, eg, Chlamydia trachomatis, Neisseria gonorrhoeae, viral infections, and bacteria from the gastrointestinal tract and the skin. The etiology of ophthalmia neonatorum is classified as either sexually transmitted bacteria, nonsexually transmitted bacteria, viral, or chemical (see Table 2. Ophthalmia Neonatorum Etiologies). 

Neisseria gonorrhea accounts for <1% of ophthalmia cases worldwide; however, in babies born to mothers infected with N. gonorrhoeae, up to 48% develop ophthalmia neonatorum; in rare cases, if untreated or inadequately treated, meningitis and septicemia may develop. Nonsexually transmitted bacteria, eg, Staphylococcus aureus, Streptococcal species, and gram-negative bacteria, as well as Haemophilus, account for 30% to 50% of ophthalmia cases. Adenovirus and herpes simplex virus are the most common causes of viral conjunctivitis.[14][9][15]

Ophthalmia neonatorum—the onset of conjunctival inflammation within the first 28 days of life—has a well-characterized spectrum of causes. Etiologies are grouped into chemical, bacterial, viral, and other infectious agents. The timing of presentation, severity of inflammation, and risk of complications vary depending on the cause.[16]

Chemical Conjunctivitis

Chemical conjunctivitis is associated with the following characteristics:

• Agents: Silver nitrate (historical), povidone-iodine, preservatives in prophylactic drops
• Onset: Within 1 to 24 hours of application
• Pathogenesis: Direct epithelial irritation leading to transient conjunctival hyperemia and tearing
• Clinical course: Mild redness and tearing, resolves in 24 to 48 hours without antimicrobial therapy [17]

Bacterial Conjunctivitis

The clinical features associated with bacterial conjunctivitis vary depending on the etiologic organism (see Table 1. Bacterial Conjunctivitis Organism Features).

Table 1. Bacterial Conjunctivitis Organism Features

Viral Conjunctivitis

 Conjunctivitis caused by viral infections is associated with the following characteristics:

• Herpes simplex virus (HSV) type 2
• Transmission: Vertical (intrapartum) or postnatal contact
• Onset: 5 to 14 days
• Features: Conjunctivitis often accompanied by eyelid vesicles, dendritic corneal ulcers, systemic signs (eg, fever and irritability)
• Complications: Corneal scarring, disseminated neonatal herpes [18]
• Enterovirus or adenovirus (rare)
• Onset: 1 to 2 weeks
• Features: Follicular conjunctivitis, watery discharge, adenopathy
• Complications: Typically self-limited; risk of keratitis [19]

Other Infectious Agents

Conjunctivitis caused by the following infectious agents is associated with these characteristics:

• Pseudomonas spp., gram-negative rods
• Context: Premature infants in neonatal intensive care, especially with indwelling devices
• Onset: Variable
• Features: Severe purulent conjunctivitis, high risk of systemic spread
• Complications: Conjunctival and corneal ulceration, sepsis [20]
• Fungal (Candida spp.)
• Context: Extremely premature or immunocompromised neonates
• Onset: Variable, often >7 days
• Features: White pseudomembranes on the conjunctiva, minimal discharge
• Complications: Membrane formation, risk of systemic candidiasis [21]

Table 2. Ophthalmia Neonatorum Etiologies

Epidemiology

Before 1880, ophthalmia neonatorum was the leading cause of permanent blindness in neonates, mainly caused by Neisseria gonorrhoeae. In 1881, Dr. Crede used 2% of silver nitrate for the first time at the time of birth for ophthalmia prophylaxis. After that time, the epidemiology of this eye disease changed, and the incidence of N. gonorrhoeae as the causal agent of ophthalmia decreased from 10% to 0.3%.[9] In the United States, ophthalmia neonatorum caused by N. gonorrhoeae has an incidence of 0.3 per 1000 live births, while Chlamydia trachomatis represents 8.2 per 1000 cases. 

Ophthalmia neonatorum—neonatal conjunctivitis occurring within the first 28 days of life—remains an important cause of infant morbidity worldwide, despite advances in prenatal care and prophylactic interventions. Its overall incidence varies significantly by region, influenced by maternal STI prevalence, access to prenatal screening, and the routine implementation of topical ocular prophylaxis after birth. In high-income countries, where universal prenatal screening for chlamydia and gonorrhea is standard and where erythromycin ointment prophylaxis is mandated, the incidence of gonococcal ophthalmia neonatorum has fallen to less than 1 case per 100,000 live births. Chlamydial conjunctivitis, though more common than gonococcal disease in these settings, is still relatively rare, affecting approximately 2 to 5 per 10,000 live births.[22]

By contrast, in low- and middle-income countries (LMICs) where STI screening during pregnancy may be limited and topical prophylaxis inconsistently applied, rates are substantially higher. Surveys in sub-Saharan Africa report neonatal conjunctivitis rates ranging from 10% to 20% of all live births, with gonococcal cases comprising up to 5% of conjunctivitis presentations and chlamydial cases often falling within the 10% to 15% range. In South Asia, studies estimate a prevalence of neonatal conjunctivitis of 8% to 12%, with gonorrhea and chlamydia each contributing roughly one-third of cases. In Latin America, neonatal conjunctivitis affects about 5% to 10% of newborns, though comprehensive surveillance data are lacking in many rural areas.[23]

The age of onset helps distinguish etiologies: chemical irritation from prophylactic agents typically arises within the first 24 hours, gonococcal infections present between days 2 and 5, chlamydial infections between days 5 and 14, and herpes simplex virus (HSV) infections after day 7. HSV ophthalmia neonatorum is comparatively rare, occurring in 1 to 2 per 100,000 births in high-resource settings, but carries a high risk of corneal scarring and visual loss if left untreated. Globally, HSV eye involvement complicates approximately 10% of neonatal HSV infections, which occur in roughly 1 in 3,000 to 1 in 5,000 live births.[24]

Risk factors for ophthalmia neonatorum mirror those for maternal infection. Mothers with inadequate prenatal care, untreated STIs, younger maternal age (<25 years), multiple sexual partners, or a history of STIs are at increased risk of transmitting infection to the newborn (Williams and Clark, 2018). Vertical transmission rates for untreated maternal gonorrhea exceed 30%, and for chlamydia can reach 50%, underscoring the critical importance of screening and treatment during pregnancy.[25]

The burden of disease is not limited to acute conjunctivitis; up to 20% of affected infants in resource-limited settings develop corneal ulceration, and 5% to 10% may suffer permanent vision loss or globe perforation if not promptly diagnosed and treated. Even mild disease can lead to parental anxiety and increased healthcare utilization. Conversely, robust prophylaxis programs—whether penicillin eye drops, erythromycin ointment, or povidone-iodine in some low-resource contexts—can reduce overall conjunctivitis rates by 50% to 70%.[17]

Consequently, the epidemiology of ophthalmia neonatorum reveals stark disparities between high- and low-resource settings. While developed nations have nearly eliminated gonococcal neonatal eye infections and reduced chlamydial cases through routine prenatal STI screening and universal prophylaxis, LMICs continue to bear a heavy burden of disease. Strengthening prenatal care, expanding access to affordable STI diagnostics and treatment, and ensuring availability of effective ocular prophylaxis at birth are essential strategies for further reducing the global incidence of this preventable cause of neonatal ocular morbidity.[26]

Pathophysiology

Ophthalmia neonatorum occurs when pathogens or irritants come into contact with the newborn’s ocular surface, overcoming innate defenses and triggering a characteristic inflammatory cascade (see Table 4. Sequence of Conjunctival and Corneal Pathophysiologic Events). In the healthy eye, the tear film and blinking help clear debris and microbes, while conjunctival epithelial cells secrete antimicrobial peptides and immunoglobulins that neutralize invaders. In the neonate, however, tear production is immature, blink reflexes may be sluggish, and the conjunctival barrier is more permeable, creating an opportunity for organisms acquired during passage through the birth canal—or, less commonly, in utero—to colonize and infect the conjunctival epithelium.[1]

Within hours of birth, chemical agents used for prophylaxis (eg, silver nitrate or povidone-iodine) can irritate the delicate conjunctiva, causing transient hyperemia and tearing. This chemical conjunctivitis is usually self-limited, but it can lay the groundwork for secondary bacterial colonization. When Neisseria gonorrhoeae is present, its pili and outer membrane proteins mediate rapid adherence to and invasion of conjunctival epithelial cells. The organism’s potent endotoxin stimulates a brisk neutrophilic infiltrate, leading to the formation of thick, purulent exudate, epithelial necrosis, and potential corneal ulceration. Capillary permeability increases sharply under the influence of locally released vasoactive mediators, resulting in the eyelids becoming markedly swollen and red by the second or third day of life. Without prompt antibiotic therapy, gonococcal conjunctivitis can progress to frank corneal perforation within 24 to 48 hours of symptom onset.[4]

Chlamydia trachomatis gains entry to conjunctival cells via endocytosis, surviving within membrane-bound inclusion bodies that house the replicative reticulate form of the organism. After a latent interval of 5 to 14 days, infected cells release elementary bodies—highly infectious particles—that infect adjacent epithelial cells. The host immune response, dominated by lymphocytes and macrophages rather than neutrophils, produces a more mucopurulent but less immediately destructive discharge than that of the gonococcus. Over weeks, repeated infection and inflammation may lead to conjunctival scarring and symblepharon formation in severe cases, although most infants develop only mild to moderate hyperemia, eyelid swelling, and a watery to mucopurulent discharge.[27]

HSV type 2, acquired transplacentally or during passage through an infected birth canal, invades corneal epithelial cells and spreads via intraepithelial and stromal processes. Infected cells lyse, and the virus elicits both innate and adaptive responses, including natural-killer cell activity and cytotoxic T-cell–mediated killing of infected epithelial cells. This immune-mediated component contributes to the formation of dendritic ulcers, stromal inflammation, and, in some instances, endotheliitis. The result can be punctate keratitis, geographic epithelial defects, or deep stromal necrosis, with risk of scarring and vision loss.[28]

Throughout these infectious processes, the neonate’s immature immune system, characterized by lower complement levels, diminished neutrophil chemotaxis, and incomplete adaptive immunity, limits the rapid clearance of pathogens. At the same time, developing tissues are highly susceptible to damage from both microbial toxins and host inflammatory mediators. Tear flow, which is sluggish in newborns, fails to dilute and effectively wash away organisms. Conjunctival lymphatics and blood vessels can carry pathogens into the nasolacrimal system and, potentially, the bloodstream, contributing to systemic infection risk in particularly aggressive cases of gonococcal or herpetic ophthalmia.[29]

The pathophysiology of ophthalmia neonatorum is characterized by the interplay between pathogen virulence factors (eg, adhesins, endotoxins, inclusion body formation, and viral replication) and the neonate’s immature ocular defenses. Whether chemical, bacterial, or viral in origin, the resulting inflammatory cascade leads to hallmark signs—chemosis, conjunctival injection, eyelid edema, and discharge—and, if unchecked, may jeopardize corneal integrity and visual development (see Table 3. Pathogen-Specific Mechanisms of Conjunctival Injury). Prompt recognition and targeted therapy are therefore essential to interrupt these processes before permanent ocular damage ensues.[1]

Table 3. Pathogen-Specific Mechanisms of Conjunctival Injury

Table 4. Sequence of Conjunctival and Corneal Pathophysiologic Events

Histopathology

On microscopic examination, the conjunctival and corneal tissues of neonates with ophthalmia neonatorum reveal features that reflect both the causative agent and the intensity of the inflammatory response (see Table 5. Pathogen-Specific Histopathologic Findings in Ophthalmia Neonatorum). Overall, histopathology in ophthalmia neonatorum highlights the pathogen-specific cellular infiltrates—neutrophilic in gonococcal infection, mononuclear in chlamydial disease, and cytopathic in herpes, underscoring the importance of rapid etiologic diagnosis and therapy to prevent progressive tissue destruction and preserve ocular integrity (see Table 6. Common Tissue Reactions and Their Microscopic Correlates).[30]

Bacterial Histological Findings

In bacterial cases—particularly those caused by Neisseria gonorrhoeae—sections of conjunctival biopsy reveal a dense, often transmucosal neutrophilic infiltrate that fills the epithelium and subepithelial stroma. Large aggregates of polymorphonuclear leukocytes accumulate within dilated lymphatic-like channels in the substantia propria, and surface epithelial cells may exhibit foci of necrosis.[7]

Gram staining typically highlights numerous intracellular and extracellular gram-negative diplococci adherent to or invading the epithelial layer. Under higher magnification, one can appreciate epithelial microabscesses—small collections of neutrophils that blur the standard epithelial architecture—and extensive epithelial sloughing. The underlying lamina propria demonstrates vascular congestion, marked endothelial cell swelling, and perivascular cuffing by neutrophils. In severe, untreated cases, organisms and inflammatory cells may extend onto the corneal surface, producing a dense epithelial defect, underlying stromal infiltration by neutrophils, and early collagen breakdown that on histology appears as stromal edema and fragmentation of Bowman’s layer.[31]

In chlamydial ophthalmia, the histopathologic picture is more lymphoplasmacytic than neutrophilic. Conjunctival epithelium shows mild to moderate hyperplasia and spongiosis, with scattered intracytoplasmic inclusion bodies—round basophilic aggregates 0.3 to 1.0 µm in diameter—visible on hematoxylin and eosin stain or highlighted by Giemsa or iodine–periodic acid–Schiff (PAS) stains. These inclusions represent the intracellular elementary-body form of the organism. The subepithelial stroma is predominantly infiltrated by mononuclear cells, including lymphocytes, macrophages, and fewer plasma cells, often in a perivascular distribution. Follicle formation may be seen, especially along the tarsal conjunctiva, where aggregated lymphocytes form germinal-center-like structures. Stromal edema is typically mild, and vascular proliferation may be noted. Chronic cases can develop early fibrotic changes, with subepithelial collagen deposition and occasional symblepharon formation.[32]

Viral Histological Findings

When ophthalmia neonatorum is caused by HSV, corneal specimens show characteristic epithelial and stromal changes. Epithelial cells exhibit ballooning degeneration, characterized by enlarged nuclei with margination of chromatin and occasional multinucleation. Intranuclear Cowdry type A inclusion bodies—eosinophilic nuclear pads surrounded by clear halos—are diagnostic of this condition. The epithelial layer may be wholly or partially denuded in areas of ulceration. Beneath the ulcer bed, neutrophils accumulate along with fibrin, and in the deep stroma, patchy necrosis is present. Keratocytes adjacent to necrotic foci may show nuclear pyknosis. Viral antigens can be confirmed by immunofluorescence or immunohistochemistry, which label viral capsid proteins within epithelial and sometimes stromal cells.[33]

Chemical Conjunctivitis Histological Findings

In chemical conjunctivitis caused by prophylactic agents, histology reveals superficial epithelial toxicity rather than an actual infection. The epithelium shows vacuolar change and superficial sloughing, but without significant inflammatory cell infiltrates. Occasional subepithelial lymphocytes may be present, and mild vascular congestion is common. Neither inclusion bodies nor detectable organisms are noted. Chemical conjunctivitis (eg, silver nitrate) shows predominantly epithelial injury rather than heavy stromal inflammation.

Across all types, the neonatal conjunctival tissue exhibits more delicate and loosely organized collagen fibers in the substantia propria than in adult tissue, which predisposes it to rapid edema. Newborn vessels are also more permeable, which explains the pronounced chemosis and edema observed microscopically.

Table 5. Pathogen-Specific Histopathologic Findings in Ophthalmia Neonatorum

Table 6. Common Tissue Reactions and Their Microscopic Correlates

Toxicokinetics

In the context of ophthalmia neonatorum, toxicokinetics refers to the process by which prophylactic and therapeutic agents applied to the neonatal eye are absorbed, distributed, metabolized, and eliminated, as well as how these processes relate to their potential for local or systemic toxicity (see Table 7. Toxicokinetic Profile of Ophthalmia Neonatorum Therapeutic Agents). Because newborn skin and mucous membranes are uniquely permeable and their metabolic pathways immature, understanding the kinetic profile of ocular agents is critical to ensure both efficacy against pathogens and safety for the infant.[34]

Absorption

Topically applied antibacterial ointments or solutions, eg, erythromycin, tetracycline, or povidone–iodine, first encounter the tear film and conjunctival mucosa. The neonatal conjunctiva is thinner and more vascular than in older children or adults, and the corneal epithelium has a higher rate of cell turnover. As a result, some fraction of the drug penetrates through the epithelium into the stroma or is absorbed directly into the systemic circulation via conjunctival blood vessels. For water-soluble agents (eg, erythromycin base in a 0.5% ointment), the drug dissolves in the tears and enters epithelial cells through passive diffusion. Lipid-soluble drugs penetrate more readily but may also linger in the lipid layers of the tear film, thereby prolonging local exposure. In contrast, ionic compounds (eg, silver nitrate) dissociate in tears and deliver antimicrobial silver ions; however, these ions can bind to tissue proteins, limiting their deeper penetration.[35]

Distribution

Once absorbed across the conjunctiva, small amounts of the drug enter the periocular capillary network and can then be distributed systemically. Neonates’ body water content is high (approximately 75% to 80% of body weight), and their plasma protein binding capacity is significantly lower than in older children, meaning that free (unbound) drug concentrations in the bloodstream can be proportionately higher for a given absorbed dose. Nonetheless, the total absorbed mass is generally very low—often in the microgram range per eye drop or ointment application—so systemic concentrations remain minimal. In the eye itself, distribution to intraocular structures, including the anterior chamber, iris, or lens, is negligible at prophylactic concentrations; most of the drug remains confined to the conjunctival surface or superficial cornea.[36]

Metabolism

Neonates have immature hepatic enzyme systems, particularly the cytochrome P450 family, and reduced phase II conjugation capacity (eg, glucuronidation). However, because ocular antibiotic ointments are often composed of drugs delivered in their active form and because very little of the applied dose is absorbed systemically, hepatic metabolism generally plays a minor role in clearance. Erythromycin, for example, if absorbed, may undergo demethylation by CYP3A enzymes, but first-pass metabolism is limited since absorption occurs into conjunctival rather than portal circulation. Silver ions from silver nitrate combine with sulfhydryl groups in proteins to form insoluble silver–protein complexes. Although no enzymatic metabolism is noted, silver may be sequestered in tissues and slowly excreted.[37]

Elimination

Drugs absorbed into the circulation are eliminated primarily by renal excretion in neonates. Renal function in newborns is immature: glomerular filtration rate in the first week of life is approximately 30% to 40% of adult levels and improves over the first few months. Consequently, any systemically absorbed erythromycin or tetracycline may have a prolonged half-life compared to adults; however, the very low absorbed quantities mean that the overall systemic burden remains negligible. Locally, elimination from the ocular surface occurs via tear turnover (rate ~0.5–2 µL/min) and nasolacrimal drainage, whereby the drug enters the nasolacrimal duct and is swallowed, exposing the gastrointestinal tract to small residual doses.[38]

Toxicity Considerations

Because the neonatal conjunctiva and cornea are more permeable and tear turnover is slower than in adults, maintaining minimal effective concentrations on the ocular surface while avoiding local irritation is paramount. Erythromycin ointment is generally well tolerated, though occasional chemical conjunctivitis—characterized by transient redness and discharge—can occur if preservatives are present or if the ointment base is hyperosmolar. Silver nitrate has historically caused significant chemical conjunctivitis and corneal irritation due to its strong oxidative effects on surface proteins, leading to the replacement of 2% silver nitrate solution with more tolerable agents.[39]

Systemic toxicity from ocular prophylaxis is exceedingly rare. In theory, absorbed erythromycin could lead to gastrointestinal upset or contribute to hypertrophic pyloric stenosis, but epidemiologic data have not demonstrated a causal relationship at ophthalmic dosing. Tetracycline ointment theoretically raises concerns for tooth discoloration or bone deposition if systemically absorbed over prolonged periods; however, short-term use in neonates does not result in clinically significant exposure. In summary, the toxicokinetics of ophthalmia neonatorum prophylaxis are characterized by predominantly local drug action with minimal systemic absorption, limited metabolism due to the small amount of absorbed dose, and rapid local elimination via tear flow and nasolacrimal drainage. Understanding these processes ensures that agents chosen for neonatal eye care maximize antimicrobial efficacy while minimizing the risk of local irritation or systemic toxicity.[40]

Table 7. Toxicokinetic Profile of Ophthalmia Neonatorum Therapeutic Agents

This toxicokinetic profile underscores why modern neonatal ocular prophylaxis emphasizes minimally absorbed, well-tolerated agents, maximizing local antimicrobial efficacy while virtually eliminating systemic risk.

History and Physical

A complete history and physical examination, including the chronological presentation of signs of conjunctivitis, is crucial but not specific for the diagnosis. The timing and characteristics of the clinical presentation of ophthalmia neonatorum may vary depending on the etiologic agent; however, specific clinical manifestations, eg, chemosis, erythema, and discharge, can be present regardless of the underlying etiology (see Table 8. Key Findings of Ophthalmia Neonatorum by Etiology).[41] 

Chlamydia trachomatis and Neisseria gonorrhoeae are transmitted at the time of delivery. When these microorganisms are suspected of causing neonatal conjunctivitis, the clinician should obtain information about maternal infections during the prenatal period. Performing adequate screening for other STIs, including the human immunodeficiency virus, is also important.[42]

The timing of symptom onset can also serve as a guide in managing these patients. Chemical conjunctivitis should be suspected in patients who present with erythema, chemosis, eyelid edema, and discharge within the first 24 hours after birth. Gonococcal conjunctivitis typically presents between 2 and 5 days; the hallmark is a thick, purulent eye discharge accompanied by significant chemosis and eyelid edema. On the other hand, ophthalmia neonatorum due to Chlamydia trachomatis typically occurs 5 to 14 days after birth; both eyes may be affected, but unilateral involvement can also occur in some cases. The eye discharge is initially copious, then becomes purulent, and it is associated with eyelid swelling.[43]

Herpes simplex conjunctivitis is uncommon, accounting for <1% of ophthalmia cases; however, it warrants suspicion in patients presenting with unilateral chemosis, serosanguineous discharge that rarely becomes purulent, accompanied by vesicular lesions surrounding the eyelids or oral ulcers, and lymphadenopathy. Identification of this condition is crucial to prevent complications, including disseminated disease and meningoencephalitis, that may be lethal if left untreated.[18]

Ophthalmia neonatorum presents within the first 28 days of life as an acute conjunctival and often corneal infection. A systematic clinical evaluation is essential for distinguishing among causative pathogens, assessing disease severity, and guiding prompt management.

Clinical History

Perinatal and maternal factors associated with ophthalmia neonatorum include:

• Timing of onset
• Early (day 1–2): Suggests chemical conjunctivitis (irritant from prophylactic agents) or Neisseria gonorrhoeae infection.
• Intermediate (Day 3–7): Most consistent with N. gonorrhoeae
• Late (day 5–14): More typical of Chlamydia trachomatis
• Maternal infections and screening
• Known or suspected maternal STIs, eg, gonorrhea, chlamydia, HSV
• Prenatal screening results, adequacy of maternal antibiotic treatment if STI diagnosed
• Prophylactic agents: Type of ocular prophylaxis at birth (eg, silver nitrate, erythromycin ointment), chemical conjunctivitis risk on day 1
• Feeding and behavior: Tolerance of feeds, irritability, and sleep disturbance may indicate systemic involvement or discomfort.
• Systemic symptoms: Fever, lethargy, poor feeding, and respiratory distress—raising concern for systemic dissemination (particularly with N. gonorrhoeae or HSV).[44]

Physical Examination

A thorough physical examination for suspected ophthalmia neonatorum includes both ocular and general examinations.

General Examination

The general examination findings may include:

• Vital signs: Temperature (fever suggests systemic spread), heart rate, respiratory rate
• Skin and mucosa: Vesicular lesions on skin or mouth (eg, HSV), rash, hepatosplenomegaly (chlamydial or gonococcal sepsis) [45]

Ocular Examination

 Findings consistent with ophthalmia neonatorum may include:

• Eyelids and periocular skin
• Swelling (chemosis), erythema, tenderness
• Presence of vesicles or ulcerations on eyelids (eg, HSV)
• Conjunctiva
• Degree and character of discharge
• Copious purulent discharge (N. gonorrhoeae)
• Mucoid or watery discharge (C. trachomatis or viral)
• Fine white, granular discharge (chemical)
• Conjunctival injection intensity
• Follicles versus papillae
• Follicles (small, translucent, central lymphoid aggregates) in chlamydia
• Papillae (raised, vascular) with bacterial infections [46]
• Cornea
• Presence of corneal clouding, epithelial defects, infiltrates, and ulceration
• Risk of perforation in gonococcal infection
• Pseudomembrane/membrane formation: Tenacious membranes that may bleed on removal (seen in C. trachomatis and severe bacterial infections)
• Lymphadenopathy: Preauricular lymph node enlargement (common in chlamydia and viral conjunctivitis) [47]

Table 8. Key Findings of Ophthalmia Neonatorum by Etiology

Special Considerations

Other assessments that should be considered during clinical evaluation include:

• Severity assessment: Evaluate corneal integrity and risk of perforation—urgent ophthalmology referral if corneal ulceration or thinning is present.
• General well-being: Poor feeding or lethargy necessitates systemic evaluation and possible hospitalization.
• Differential diagnoses: Blepharitis, lacrimal duct obstruction (epiphora with minimal discharge), staphylococcal conjunctivitis.[48]

Clinical Pearls

Notable factors that clinicians should bear in mind when evaluating ophthalmia neonatorum include:

• Always correlate the timing of onset with likely pathogens.
• A “bright red eye with thick pus” in a day 3 to 5 neonate mandates immediate gram stain and culture for gonococcus.
• Persistent, follicular conjunctivitis beyond day 7 with minimal purulence suggests chlamydia—treat presumptively.
• HSV involvement is often accompanied by vesicular lesions elsewhere; treat with systemic antivirals.[49]

A structured history and meticulous ocular examination expedite pathogen-directed therapy, reduce the risk of complications (eg, corneal perforation and conjunctival scarring), and guide appropriate systemic workup in neonates with ophthalmia neonatorum.

Evaluation

When ophthalmia neonatorum is suspected, confirmation of the etiology is warranted. A sample from the eye discharge should be taken and sent for gram stain and culture in Thayer-Martin media and chocolate agar, especially if N gonorrhoeae is the possible causal agent; this guarantees that proper treatment is given and thus, ensures the prevention of potential complications which, is essential for a good prognosis and outcome. In Chlamydia trachomatis infection, polymerase chain reaction (PCR), direct fluorescent antibody staining, and Giemsa-stained epithelial cells from conjunctival scrapings can aid in making the diagnosis.[7]

Some authors have recommended nucleic acid amplification tests (NAATs) from conjunctival swabs when chlamydial ophthalmia is suspected; however, these tests do not have Food and Drug Administration approval for the detection of chlamydia in the conjunctiva. For herpetic conjunctivitis, the standard diagnostic tests for isolating the virus include viral culture and PCR-based detection of viral DNA. Patients with signs of systemic infection who appear unwell may have a disease that has spread, manifesting as meningitis, bacteremia, arthritis, or sepsis. In such cases, additional investigation, including blood culture and cerebrospinal fluid analysis for gram stain, is warranted.[50]

A structured, multistep evaluation is essential for accurately diagnosing and managing ophthalmia neonatorum, thereby minimizing the risk of vision-threatening complications and systemic spread. The evaluation encompasses a detailed clinical assessment, point-of-care diagnostics, laboratory confirmation, and targeted systemic work-up when indicated.

Detailed Clinical Assessment

Detailed clinical assessment and point-of-care diagnostic testing include the following evaluation steps (see Table 9. Bedside Point-of-Care Testing): 

• Onset and chronology
  • Chemical conjunctivitis: typically appears within the first 24 hours of life, often mild and transient, following prophylaxis with silver nitrate or erythromycin.
  • Gonococcal infection: typically emerges between days 2 and 5, characterized by a rapid onset of marked purulent discharge.
  • Chlamydial conjunctivitis: typically develops insidiously over days 5 to 14, presenting with mucoid or mucopurulent discharge and eyelid swelling.
  • Viral (HSV): involvement arises days 5 to 12 and may manifest with vesicular eyelid lesions, serous to purulent discharge, and corneal dendrites.[51]
• Symptom and sign severity
  • Discharge character: watery, mucoid, purulent
  • Conjunctival appearance: chemosis, membrane/pseudomembrane formation
  • Corneal status: inspect for clouding, epithelial defects, ulceration
  • Eyelid lesions: vesicles suggest HSV
  • Regional lymphadenopathy: preauricular nodes can enlarge in chlamydial or viral cases
  • General health: fever, irritability, and feeding difficulty may indicate systemic involvement [47]

Table 9. Bedside Point-of-Care Testing

Clinical interpretation

A positive gram or Giemsa stain prompts immediate pathogen-specific treatment. Negative results with heavy inflammation suggest viral or chemical causes, guiding further testing.[52]

Laboratory Confirmation

Culture studies

Pathogen cultures are a diagnostic component utilized to identify potential underlying etiologies of ophthalmia neonatorum (see Table 10. Culture Methods).

Table 10. Culture Methods

Molecular Diagnostics

PCR panels targeting Neisseria gonorrhoeae, Chlamydia trachomatis, and HSV allow for direct application to swabs, enabling rapid (within 48 hours) and highly sensitive detection. Direct fluorescent antibody testing or enzyme immunoassay also provides identification of chlamydial elementary bodies in epithelial cells, typically within 1 to 2 days.[53]

Ancillary and Systemic Evaluation

Further evaluation is indicated in cases involving severe purulent conjunctivitis, systemic signs, corneal ulceration, or suspected HSV encephalitis. Blood cultures and a complete blood count help assess for sepsis, especially in suspected gonococcal infections. Liver and renal function tests, along with cerebrospinal fluid analysis, assist in evaluating HSV cases presenting with neurologic symptoms. A chest x-ray may be warranted when systemic gonococcal dissemination is suspected. Furthermore, maternal medical records should be reviewed to confirm STI screening and treatment history, including testing for HSV.[54]

Imaging and Ophthalmic Examination

Slit-lamp biomicroscopy, when available and used with a neonatal speculum, can detect corneal epithelial defects, dendritic lesions, or deeper ocular involvement. Direct ophthalmoscopy, especially in severe or bilateral presentations, may uncover retinal hemorrhages or endophthalmitis.[55]

Diagnostic and Management Algorithm

The following diagnostic steps are recommended when managing a patient with suspected ophthalmia neonatorum:

1. Begin with a thorough history and confirmation of perinatal prophylaxis and symptom onset.
2. Perform bedside microscopy (gram, Giemsa, or Tzanck stain) to guide initial treatment rapidly.
3. Initiate empiric therapy based on the suspected pathogen: IM or IV ceftriaxone for Neisseria gonorrhoeae, oral azithromycin for Chlamydia trachomatis, or IV acyclovir for HSV.
4. Simultaneously obtain cultures and PCR to confirm the diagnosis and refine treatment.
5. Conduct systemic evaluations—including CBC, blood cultures, CSF analysis, and organ function panels—when clinical findings warrant further investigation.
6. Monitor clinical response daily, focusing on discharge quality, conjunctival inflammation, and corneal healing.[9]

Key Decision Points

Urgent referral to ophthalmology becomes necessary when corneal involvement, pseudomembranes, or any threat to vision is identified. Hospital admission ensures proper IV therapy for systemic gonococcal or HSV infections. Outpatient management remains appropriate for mild chlamydial conjunctivitis, provided close follow-up is arranged.

Through this layered approach—combining precise history, bedside cytology, culture, molecular testing, and systemic assessment—clinicians can accurately identify the causative pathogen, promptly initiate targeted therapy, and mitigate the ocular and systemic risks associated with ophthalmia neonatorum.

Treatment / Management

Patients with suspected neonatal conjunctivitis should be managed based on initial clinical assessment and evaluation of possible complications. Suppose the clinician has a high suspicion of neonatal conjunctivitis, but confirmatory tests for the infection are not available. In that case, treatment against both (Chlamydia trachomatis and Neisseria gonorrhoeae) should start to avoid complications.[9]

If the clinician has established the diagnosis of gonococcal ophthalmia neonatorum, immediate initiation of treatment, including hospitalization, is crucial. The first-line treatment of choice is a single dose of ceftriaxone 25 to 50 mg/kg/24 hr, with a maximum of 125 mg. Frequent eye irrigation with sterile isotonic saline is also recommended as an adjunct therapy. An alternative regimen is cefotaxime 100 mg/kg in a single dose. If chlamydial conjunctivitis is confirmed, oral erythromycin at 50 mg/kg every 24 hours for 2 weeks remains the regimen of choice; topical erythromycin can also be used as adjunctive therapy. Conjunctivitis secondary to Staphylococcal species and Pseudomonas requires treatment with systemic antibiotics. On the other hand, patients with herpes simplex conjunctivitis should receive treatment with systemic antiviral therapy, in addition to topical ophthalmic drugs, including 0.15% ganciclovir or 1% trifluridine, for 14 days. An ophthalmology consult is necessary in these cases.[56][57][58]

Recommendations about management in asymptomatic babies born to mothers infected with Chlamydia trachomatis infection exist; these babies require close monitoring for the appearance of clinical symptoms suggestive of chlamydia ocular or respiratory infections. Oral erythromycin is not recommended in asymptomatic babies due to an increased risk of developing pyloric stenosis.[59](B2)

Ophthalmia neonatorum is a potentially sight-threatening conjunctivitis that occurs in the first month of life. Immediate recognition and institution of appropriate therapy markedly reduce the risk of corneal damage, systemic complications, and long-term visual sequelae. Management must be tailored to the most likely etiological agent—chemical, bacterial (particularly Neisseria gonorrhoeae and Chlamydia trachomatis), or viral (herpes simplex virus)—and guided by local and international standards of care (see Table 10. First-Line Treatment for Common Causes of Ophthalmia Neonatorum). An interprofessional approach involving neonatologists, ophthalmologists, pediatric infectious disease specialists, and nursing staff is essential to ensure prompt diagnosis, adherence to treatment, and follow-up.[60]

Initial Assessment and Supportive Care

Upon presentation, the neonate’s general health status should be assessed, including vital signs, hydration, feeding tolerance, and signs of systemic infection. Before instituting pathogen-specific therapy, the following supportive measures should be performed to help maintain ocular comfort and hygiene:

• Eyewash and gentle cleansing: Using sterile saline or preservative-free artificial tears to remove purulent discharge and crusting from the eyelids and lashes 2 to 4 times daily aids in comfort and allows for more precise visualization of the conjunctiva and cornea.
• Lid hygiene: Soft cotton swabs dipped in sterile saline can gently cleanse the eyelid margins, decreasing bacterial load. Avoid povidone-iodine or harsh antiseptics on the newborn’s delicate skin.
• Lubrication: For cases with corneal epithelial compromise, frequent application of preservative-free ocular lubricants (drops or gels) helps protect the cornea and promotes healing.[61]

These measures do not substitute for antimicrobial therapy but create optimal conditions for drug penetration and reduce the risk of secondary skin irritation.

Etiology-Directed Antimicrobial Therapy

Gonococcal conjunctivitis (Neisseria gonorrhoeae)

Gonococcal ophthalmia neonatorum is a medical emergency due to rapid corneal infiltration and risk of perforation within 24 to 48 hours. Current international guidelines recommend the following:

• Systemic therapy: Administer a single intramuscular dose of ceftriaxone (25 to 50 mg/kg, maximum 125 mg), ensuring adequate serum and ocular tissue levels. If ceftriaxone is unavailable, cefotaxime 50 mg/kg can be administered intramuscularly (IM) or intravenously (IV).

• Topical therapy: High-concentration topical antibiotics, eg, 1% aqueous ceftriaxone or 0.5% aqueous penicillin drops, are instilled every 2 hours around the clock until clinical improvement is achieved. Then, they are instilled every 4 hours for an additional 2 to 3 days.

• Hospitalization: Due to the risk of systemic dissemination (eg, arthritis and meningitis), inpatient care with intravenous antibiotics (eg, ceftriaxone 50 mg/kg daily) may be warranted if a concern for sepsis or inadequate outpatient follow-up is present.

• Follow-up: Daily ophthalmic examinations until resolution of purulence and corneal epithelial defects.[62]

Chlamydial conjunctivitis (Chlamydia trachomatis)

Chlamydia–associated ophthalmia develops more gradually and often presents after the first week of life. Treatment entails the following:

• Systemic macrolide: Oral azithromycin 20 mg/kg as a single dose, repeated once after 1 week, has become the preferred regimen due to its excellent tolerability and high compliance. Alternative regimens include erythromycin 50 mg/kg/day divided into 4 doses for 14 days, though this carries a risk of infantile hypertrophic pyloric stenosis.

• Topical silver nitrate or erythromycin ointment: Not effective as monotherapy for chlamydia, but may be continued for symptom relief.

• Maternal and partner therapy: Simultaneous treatment of the mother (azithromycin 1 g orally) and sexual partners is essential to prevent reinfection.

• Monitoring: Clinicians should assess the resolution of conjunctivitis within 7 to 14 days; if persistent, confirm compliance and consider a second course or an alternative macrolide.[63]
(A1)

Herpes simplex virus (HSV) conjunctivitis

HSV–related disease can threaten both ocular and systemic health. Management includes:

• Systemic antiviral: Intravenous acyclovir (20 mg/kg every 8 hours) for 14 to 21 days if disseminated disease or corneal involvement is present; for isolated ocular disease, some experts recommend oral acyclovir (20 mg/kg 4 times daily for 14 days).
• Topical antiviral: Trifluridine 1% eye drops 5 times daily or vidarabine ointment 5 times daily for 10 to 14 days, in conjunction with systemic therapy, to inhibit viral replication at the ocular surface.
• Supportive measures: Frequent lubrication, antiviral mittens to prevent self-inoculation, and close monitoring for corneal dendritic lesions or stromal keratitis.
• Consultation and follow-up: Early involvement of a pediatric infectious disease specialist and serial ophthalmic exams to detect progression to keratitis or uveitis.[64]

Adjunctive and Preventive Strategies

Preventive measures are also a component of management for ophthalmia neonatorum (see Table 11. Adjunctive and Specialized Therapies). Universal prophylaxis using erythromycin 0.5% ointment, tetracycline 1% ointment, or povidone-iodine 2.5% solution, applied to both eyes within the first hour after birth, remains standard practice in many regions and effectively reduces gonococcal transmission.

Prenatal screening for gonorrhea, chlamydia, and genital herpes during the third trimester enables timely treatment of maternal infections before delivery, significantly lowering the risk of neonatal transmission. Parental counseling should include guidance on proper hand hygiene, avoiding contaminated bathing supplies, and seeking prompt medical care for any signs of recurrent ocular discharge.[35]

Management of Complications

Treatment of ophthalmia neonatorum can be associated with various complications (see Table 11. Adjunctive and Specialized Therapies). Management of these complications includes:

• Corneal ulceration and scarring
  • Treatment involves intensive antimicrobial therapy based on the identified pathogen, combined with adjunctive cycloplegia and frequent ocular lubrication to enhance comfort and support corneal healing.
  • Surgical intervention may be necessary in cases of impending corneal perforation, with options including conjunctival flap placement or therapeutic penetrating keratoplasty, performed in consultation with a pediatric corneal surgeon.[65][66]
(B3)

• Membrane or pseudomembrane formation: Mechanical removal under topical anesthesia in an operating theater helps prevent symblepharon formation. Follow-up with topical corticosteroids reduces inflammation and supports tissue recovery.[39][67]
(A1)

• Secondary glaucoma or uveitis: 
  • Topical intraocular pressure–lowering agents suitable for neonates (eg, brinzolamide) may be used alongside carefully monitored topical corticosteroids.
  • Referral to a pediatric glaucoma specialist becomes essential when medical therapy alone fails to achieve adequate control.[68][69]

Discharge Planning and Follow-Up

Before discharge, ensure caregivers understand the administration schedules, warning signs (eg, increased redness, discharge, or feeding difficulty), and the importance of follow-up visits. A typical follow-up schedule may include:

• Day 2 to 3 posttreatment initiation for clinical assessment.
• Weekly visits until complete resolution of conjunctivitis and corneal epithelial defects.
• Monthly vision and ocular health checks for the first 6 months if significant ocular involvement occurred.[70]
(B2)

Quality Improvement and Guidelines

Adherence to national and international guidelines from reputable entities, including the World Health Organization, the American Academy of Pediatrics, and the Centers for Disease Control and Prevention, ensures adherence to best practices. Continuous quality improvement initiatives—tracking rates of ophthalmia neonatorum, timing of prophylaxis, and treatment outcomes—help institutions refine protocols and reduce incidence.

Effective management of ophthalmia neonatorum hinges on a rapid etiological diagnosis, the prompt institution of targeted systemic and topical therapy, and vigilant follow-up to prevent complications. A coordinated, evidence-based approach—integrating obstetric screening, neonatal prophylaxis, interprofessional collaboration, and caregiver education—safeguards newborn vision and lays the foundation for healthy ocular development.[71](B2)

Table 10. First-Line Treatment for Common Causes of Ophthalmia Neonatorum

Table 11. Adjunctive and Specialized Therapies

Differential Diagnosis

Ophthalmia neonatorum—conjunctival inflammation occurring within the first 28 days of life—has a broad differential, encompassing both infectious and noninfectious etiologies (see. Table 12. Ophthalmia Neonatorum Differential Diagnoses) Early recognition of the specific cause is critical, as some agents (notably Neisseria gonorrhoeae and herpes simplex virus) can lead to rapid corneal damage and vision loss if not treated promptly.

Table 12. Ophthalmia Neonatorum Differential Diagnoses

Pertinent Studies and Ongoing Trials

The following summary highlights key studies and ongoing clinical trials that shape current recommendations for preventing and treating ophthalmia neonatorum. The focus centers on antibiotic prophylaxis and treatment strategies targeting the most common bacterial pathogens—Neisseria gonorrhoeae and Chlamydia trachomatis—alongside emerging therapeutic approaches.

Epidemiology of Ophthalmia Neonatorum: A Systematic Review and Meta-analysis

This global systematic review pooled data from 25 studies encompassing over 1.1 million births and found an overall incidence of ophthalmia neonatorum of 2.0% and a prevalence of 7.8%. Staphylococcus species accounted for 39% of positive cultures, while Serratia marcescens was also prominent. Alarmingly, more than 90% of S. aureus and 100% of E. coli isolates were penicillin-resistant, underscoring the need for effective universal prophylaxis to prevent vision-threatening sequelae.[8]

Ophthalmia Neonatorum in Central Ghana: Causative Agents and Antibiotic Susceptibility

In a prospective, multicenter study of 110 neonates over 17 months, bacterial pathogens were isolated in 52.4% of cases; Staphylococcus spp. Predominated (39.2%), and no Neisseria gonorrhoeae was found. Notably, 73% of isolates were tetracycline-resistant, which challenges the efficacy of standard prophylactic ointments and prompts calls for routine culture and sensitivity testing in similar settings.[72]

National Survey of Neonatal Prophylaxis Practices in Italy

Surveying 419 maternity centers covering over 1 million annual births, 82.3% of Italian newborns received ocular prophylaxis, but only 0.4% received WHO-recommended agents. Over the 3 years, 12 cases of chlamydial ophthalmia neonatorum and zero cases of gonococcal infection were reported. The findings, alongside low prenatal STI screening rates, led to the development of an intersociety guideline standardizing prophylaxis to optimize prevention and resource utilization.[73]

Chlamydial Ophthalmia Neonatorum in Botswana: Case Series and Review 

Among infants born to untreated chlamydia-positive mothers, 12 cases of ON (8 PCR-confirmed) were identified despite routine tetracycline ointment prophylaxis. Four infants developed chlamydial pneumonia, and several cases persisted after maternal erythromycin therapy. The study highlights the inadequacy of current prophylaxis alone and recommends routine prenatal chlamydia screening and treatment to avert neonatal infection.[70]

Risk of Invasive Infection in Neonates With Ophthalmia Neonatorum

Retrospectively reviewing 52 term neonates presenting with ophthalmia neonatorum in an emergency setting, investigators found no instances of concurrent invasive bacterial infection (0%, 95% CI 0–6.9%). However, evaluation and treatment practices varied widely, with 87% receiving antibiotics. The authors suggest deescalating extensive sepsis workups in healthy neonates while still ensuring prompt ocular care.[17]

Neonatal Herpes Simplex Virus Infections in Germany: 2-Year Surveillance

A nationwide surveillance study conducted from 2017 to 2018 identified 37 cases of neonatal HSV (incidence is approximately 2.35/100,000 births). Most infants had mild or no symptoms and recovered fully, but 4 suffered severe neurological impairment and 2 died. Notably, most transmissions were postnatal from family members’ orolabial lesions rather than maternal genital disease, underscoring the need for family-member education alongside maternal screening.[74]

Treatment Planning

Management of ophthalmia neonatorum hinges on prompt recognition, appropriate empiric therapy, targeted treatment once causative organisms are identified, and careful follow-up to prevent complications. The following step-wise plan reflects current international guidelines and best practices approaches (see Table 13. Prophylaxis and Initial Empiric Therapy and Table 14. Targeted Therapy and Follow-Up).

Universal Prophylaxis at Birth

Apply a topical prophylactic agent within the first hour of life. Recommended options include:

• Erythromycin ophthalmic ointment (0.5%–1%) applied once to each eye.

• Povidone–iodine solution (1.25%–2.5%) as a single drop in each eye, especially when erythromycin is unavailable or resistance is a concern.

The rationale behind this recommendation is that prophylaxis significantly lowers the risk of gonococcal and chlamydial conjunctivitis without causing systemic adverse effects.[4]

Early Recognition and Diagnostic Evaluation

Clinicians should evaluate any neonate presenting within the first month of life with symptoms suspicious for ophthalmia neonatorum, including eyelid edema, purulent discharge, conjunctival injection, or signs of corneal involvement.

Before initiating topical therapy, the conjunctival discharge should be swabbed for Gram stain, culture, sensitivity testing (including testing for Neisseria gonorrhoeae and Chlamydia trachomatis), and PCR when available. Furthermore, clinicians should review maternal history for sexually transmitted infections, prolonged rupture of membranes, or intrapartum infections.[16]

Empiric (Initial) Therapy

Gonococcal coverage

For symptoms emerging 2 to 5 days after birth with highly purulent discharge, initiate immediate treatment for gonorrhea while awaiting culture results, consisting of ceftriaxone IV or IM at 25 to 50 mg/kg (maximum dose 125 mg), due to its rapid corneal penetration and favorable resistance profile.

Chlamydial coverage

For symptom onset between 5 and 14 days featuring mucopurulent discharge without marked conjunctival swelling, oral azithromycin at 20 mg/kg as a single dose, or erythromycin at 50 mg/kg/day divided into 4 daily doses for 14 days should be prescribed.

Combination cases or unclear etiology

In patients with unclear underlying etiologies or a combination of Neisseria gonorrhoeae and Chlamydia trachomatis, both ceftriaxone (single dose) and oral azithromycin (single dose) should be used to ensure coverage for both pathogens.[11] 

Targeted (Organism-Specific) Therapy

For confirmed Neisseria gonorrhoeae infections, treatment requires a 7- to 10-day course of a systemic third-generation cephalosporin, eg, cefotaxime or ceftriaxone. Daily saline eye irrigation should continue until ocular discharge fully resolves. In cases involving Chlamydia trachomatis, oral erythromycin or azithromycin should be continued for the entire 14-day regimen.

To prevent recurrence, retesting and appropriate treatment of the mother and her sexual partner should be undertaken. When other organisms, eg, Staphylococcus or HSV, are identified, therapy must be guided by culture or PCR results, which may include topical fortified antibiotics or acyclovir, depending on the pathogen involved.[45]

Supportive Measures

Frequent and gentle saline irrigation of the eyes helps remove purulent discharge and maintain eyelid hygiene. Daily slit-lamp examinations are necessary to monitor for corneal involvement, eg, keratitis or ulceration. Upon detection of corneal changes, escalation of the antimicrobial regimen and possible hospital admission should be promptly considered to prevent permanent ocular damage.[17]

Follow-Up and Prevention of Sequelae

Ongoing inpatient care should include daily ophthalmology consultations until the patient demonstrates marked clinical improvement. Outpatient follow-up must occur at 1 week and again at the conclusion of therapy to confirm complete resolution and to identify any complications, eg, corneal scarring or vision impairment. Screening of the mother and her sexual contacts for N. gonorrhoeae and C. trachomatis remains essential, and any positive cases require full treatment to break the cycle of reinfection.[46]

Reporting and Public Health Measures

Confirmed diagnoses of N. gonorrhoeae or C. trachomatis must be reported to local public health authorities in compliance with regulatory requirements. Parental education plays a vital role in preventing recurrence; caregivers should receive clear instructions on maintaining hygiene, recognizing signs of relapse, and completing the full course of systemic treatment.

By systematically following this protocol—from universal prophylaxis through targeted therapy and vigilant follow-up—clinicians can effectively prevent, diagnose, and manage ophthalmia neonatorum, thereby safeguarding neonatal ocular health and preserving vision.[60]

 Table 13. Prophylaxis and Initial Empiric Therapy

Use a combined regimen if awaiting diagnostics or are at high risk for mixed infection.

Table 14. Targeted Therapy and Follow-Up

Expanded Treatment Planning

Universal prophylaxis

Prophylactic ocular instillation at birth is universally recommended to prevent gonococcal and chlamydial conjunctivitis. Erythromycin ophthalmic ointment remains the first choice due to its proven safety and efficacy. In resource-limited settings or during drug shortages, a single drop of dilute povidone–iodine provides broad-spectrum antimicrobial coverage without the risk of antibiotic resistance.

Early recognition and diagnostics

Any neonate presenting within the first month with eyelid swelling and conjunctival discharge should prompt immediate evaluation. Before topical therapy, swab the conjunctival sac for gram stain, culture, and PCR to guide therapy.

Empiric therapy

For suspected gonococcal infections (onset 2–5 days), a single dose of ceftriaxone is administered, given the risk of rapid corneal ulceration. For later-onset, more indolent chlamydial cases, oral macrolide antibiotics are started. If the causative organism is unclear or dual infection is likely, combined coverage with both agents is prudent.

Targeted therapy

Once culture or PCR identifies the pathogen, antimicrobials are tailored accordingly. Gonococcal cases require extended systemic treatment with third-generation cephalosporins; chlamydial infections require a full course of macrolides. For other bacterial, viral, or fungal pathogens, modify therapy based on susceptibility data and clinical response.

Supportive measures

Frequent saline irrigations and proper eyelid hygiene help prevent the accumulation of biofilm and facilitate the penetration of medications. Corneal integrity must be monitored daily; severe cases often warrant inpatient care until the risk of ulceration resolves.

Follow-up

Structured follow-up ensures infection clearance and early detection of sequelae, eg, corneal scarring, symblepharon, or vision impairment. Maternal and partner screening for STIs completes the cycle of care and prevents the risk of reinfection.

By combining universal prophylaxis, prompt empiric therapy, organism-specific treatment, and meticulous follow-up, this comprehensive treatment plan aims to eliminate ophthalmia neonatorum pathogens, prevent sight-threatening complications, and safeguard long-term visual outcomes in newborns.

Toxicity and Adverse Effect Management

While the cornerstone of therapy for ophthalmia neonatorum is prompt antimicrobial treatment, clinicians must remain vigilant for potential toxicities and adverse reactions associated with systemic and topical agents used in newborns (see Table 15. Common Neonatal Adverse Effects and Management of Systemic and Topical Therapeutic Agents). Common adverse effects and evidence-based strategies to prevent or manage them vary depending on the therapeutic agent used.

Table 15. Common Neonatal Adverse Effects and Management of Systemic and Topical Therapeutic Agents

Key Management Principles

Parental counseling should precede the start of treatment to address expected side effects, eg, mild ocular stickiness from topical ointments or gastrointestinal discomfort following the use of oral antibiotics. Setting these expectations helps build trust and promotes better adherence to the therapeutic regimen.

Weight-based dosing and strict adherence to recommended treatment durations remain critical to minimizing systemic toxicity. Prolonged erythromycin use, for example, may increase the risk of developing complications such as pyloric stenosis, particularly in neonates.

When significant adverse effects arise, switching to an alternative medication within the same drug class may be necessary. For instance, azithromycin may be used as an alternative to erythromycin for chlamydial infections, or cefotaxime may serve as an alternative to ceftriaxone for gonococcal coverage, with culture data guiding these substitutions.

Daily ocular examinations help detect early signs of epithelial toxicity in severe cases. In addition, clinicians should closely observe feeding behavior, track weight gain, and monitor stool patterns during systemic antibiotic use. For IM therapy, injection sites require assessment for erythema, tenderness, or induration to identify local complications promptly.

By anticipating these potential toxicities, educating caregivers, and promptly addressing adverse reactions, clinicians can optimize the safety profile of ophthalmia neonatorum treatments while preserving their efficacy in preventing sight-threatening sequelae.[80]

Staging

Ophthalmia neonatorum is typically staged by the time of onset after birth, which correlates closely with the most common etiologies. Early recognition of the timing of disease onset helps guide diagnostic evaluation and empirical therapy.

*Many jurisdictions now use antibiotic eye ointment (eg, erythromycin) instead of silver nitrate; true “chemical” conjunctivitis has become uncommon, but staging retains historical importance.

Clinical Application of Ophthalmia Neonatorum Staging

Accurate identification of disease stage based on symptom timing and clinical presentation supports targeted empiric treatment while awaiting microbiologic confirmation. This approach minimizes the risk of vision-threatening complications and improves long-term visual outcomes in affected neonates.

Empiric therapy

Stage II onset requires immediate intervention, including gram staining and culture, as well as IV or IM administration of a third-generation cephalosporin, due to the potential for rapid corneal perforation. Clinical signs consistent with stage III should prompt oral macrolide therapy following appropriate swab collection. In cases of Stage IV presentation, severe disease warrants HSV PCR or Tzanck smear testing and intravenous acyclovir administration.[81]

Diagnostic evaluation

Conjunctival swabs should be obtained in stages II through V to perform gram staining, culture, and PCR testing based on clinical suspicion and availability. These diagnostic tools help identify the causative organism and guide targeted antimicrobial therapy.

Systemic involvement must be excluded when evaluating for gonococcal and herpetic infections. In such cases, a thorough clinical assessment and additional laboratory testing help determine the extent of the disease and ensure timely intervention to prevent serious complications.[82]

Prognosis

Stage I typically results in excellent outcomes without long-term sequelae. Prompt recognition and supportive care contribute to complete recovery in nearly all cases. Stage II presents the highest risk for corneal scarring and demands aggressive intervention to preserve ocular integrity. Early administration of appropriate systemic antibiotics and close ophthalmologic monitoring remain essential to prevent serious complications.

Stage III often responds favorably to macrolide therapy when initiated without delay. Timely treatment reduces the likelihood of associated nasopharyngeal colonization or secondary complications. Stage IV, if left unrecognized or untreated, may progress to chronic conjunctival scarring and permanent vision loss. Early detection and initiation of antiviral therapy are critical to mitigate these outcomes.[28]

Prognosis

Before 1880, ophthalmia neonatorum due to Neisseria gonorrhoeae was the most common cause of neonatal blindness. Early detection and timely treatment of infected mothers are crucial elements in preventing permanent ocular damage. If left untreated or partially treated, corneal ulceration, perforation, and blindness can occur. Approximately 10000 cases of blindness per year are secondary to ophthalmia neonatorum worldwide. Fortunately, in most cases, neonatal ophthalmia neonatorum caused by nongonococcal bacteria is a mild disease with a good prognosis. However, up to 50% of babies born to mothers with chlamydia infection may develop neonatal conjunctivitis, and among those, between 10% and 20% are at risk of developing pneumonia. Chemical conjunctivitis secondary to silver nitrate is self-limiting.[56][51][83]

The visual and systemic outlook for a neonate with ophthalmia neonatorum varies significantly depending on the etiology, timeliness of recognition, and appropriateness of therapy. Early and accurate diagnosis, along with the institution of targeted treatment, are critical for preventing long-term ocular morbidity. The following prognostic outcomes are associated with each etiology:

• Chemical conjunctivitis (stage I)
  • Visual outcome: Excellent; virtually no risk of corneal involvement or scarring once irritant removed
  • Course: Self-limited within 24 to 48 hours after cessation of the causative agent
  • Sequelae: None [9]

• Gonococcal conjunctivitis (stage II)
  • Visual outcome: Guarded without prompt treatment. Historical data report up to 20% risk of corneal ulceration, perforation, and potential blindness if therapy is delayed beyond 24 hours.
  • Following aggressive therapy: Intravenous or intramuscular third-generation cephalosporins reduce corneal complications to under 5%. Timely intervention often preserves normal vision.
  • Systemic risks: May develop concurrent septic arthritis or meningitis in up to 10% of untreated infants; early systemic antibiotic treatment minimizes these risks [5]

• Chlamydial conjunctivitis (stage III)
  • Visual outcome: Generally favorable when treated with a full course of systemic macrolides (eg, oral erythromycin or azithromycin)
  • Corneal involvement: Rare; mild punctate keratitis can occur but typically resolves without scarring
  • Late sequelae: Without treatment, chronic follicular conjunctivitis may persist for weeks to months, but permanent damage is uncommon [84]

• Herpes simplex conjunctivitis (stage IV)
  • Visual outcome: Variable. Corneal ulceration may lead to scarring and astigmatism; early administration of IV acyclovir and ophthalmic antivirals improves the prognosis.
  • Systemic outcome: Neonatal HSV disseminated disease carries 30% to 50% mortality without treatment. With timely antiviral therapy, mortality falls below 10%, though neurological sequelae remain a concern.
  • Long-term: Survivors require lifelong ophthalmic follow-up to monitor for potential recurrent keratitis and scarring.[18]

• Other bacterial pathogens (stage V)
  • Visual outcome: Generally good when treated with culture-guided topical antibiotics; purulent infections caused by Staph or Streptococcus rarely result in corneal perforation.
  • Complications: Pseudomonas species infections can progress rapidly; however, early antibiotic therapy typically prevents severe complications from developing.[85]

Factors Influencing Prognosis

Several key factors influence the prognosis of ophthalmia neonatorum, each carrying significant weight in determining clinical outcomes. 

Time to treatment plays a critical role, particularly in cases involving suspected gonococcal or herpetic infections. Delays, even by a few hours, substantially elevate the risk of corneal damage, underscoring the need for immediate empiric intervention upon suspicion. Additionally, access to care also shapes prognosis. In low-resource settings, the absence of routine ocular prophylaxis and limited availability of effective antibiotics often leads to more severe disease progression and poorer visual outcomes. Strengthening healthcare infrastructure and ensuring consistent prophylactic practices can improve prognosis in these environments.

Furthermore, compliance with the full antibiotic course and adherence to scheduled ophthalmic follow-ups significantly reduce the likelihood of chronic ocular sequelae. Continued monitoring helps detect residual inflammation or complications such as corneal scarring early in the disease course. Systemic evaluation becomes essential in cases involving potential dissemination, especially with gonococcal or herpetic pathogens. Coordinated interprofessional care supports both survival and neurological function by addressing systemic involvement in conjunction with ocular management.[86]

With modern prophylaxis and prompt, pathogen-directed therapy, the vast majority of cases of ophthalmia neonatorum resolve without lasting visual impairment. Gonococcal and herpetic infections remain the most severe threats; aggressive early treatment and careful monitoring are essential to preserve sight and overall health.

Complications

Untreated ophthalmia neonatorum places infants at high risk for severe complications, including corneal ulceration, perforation of the ocular globe, and irreversible blindness. In rare instances, the infection may extend beyond the ocular surface, leading to meningitis, sepsis, or death.

Inadequate prevention or delayed treatment can result in a wide range of complications. Some infants may experience mild conjunctival scarring, while others may progress to significant vision loss due to corneal involvement. Certain pathogens, eg, Neisseria gonorrhoeae and herpes simplex virus, pose a heightened risk for systemic dissemination.

Prompt identification of clinical signs and initiation of targeted therapy remain essential to prevent irreversible damage. Aggressive management, especially during the early stages, reduces the likelihood of ocular morbidity and improves long-term visual and systemic outcomes (see Table 17. Long-Term Sequelae and Management Strategies). Complications of ophthalmia neonatorum include:

• Corneal involvement
  • Punctate keratitis: Fine epithelial defects that cause irritation but rarely scar if treated promptly.[87]
  • Corneal ulceration: Full-thickness epithelial and stromal loss; risk is highest with Neisseria gonorrhoeae and Pseudomonas (see Table 16. Ocular Complication Rates by Pathogen).[88]
  • Corneal perforation: Extreme ulcerative progression may breach the corneal stroma, necessitating emergency surgical repair.[89]
• Conjunctival scarring and symblepharon: Chronic inflammation—especially from untreated chlamydial or herpetic infections—can lead to subconjunctival fibrosis, forniceal shortening, and adhesions between bulbar and palpebral conjunctiva.[47]
• Secondary glaucoma: Scarring around the ocular surface or angle structures may impede aqueous outflow, leading to elevated intraocular pressure and damage to the optic nerve.[90][91][92]
• Visual axis opacification: Persistent epithelial defects or stromal scarring centrally may decrease best-corrected acuity and induce irregular astigmatism.[93]
• Structural dyelid and lacrimal sequelae
  • Cicatricial entropion or trichiasis from conjunctival fibrosis can abrade the cornea.
  • Scarring of the puncta or canaliculi may cause chronic epiphora and predispose to dacryocystitis.[94]
• Systemic spread
  • Neisseria gonorrhoeae: Risk of bacteremia, septic arthritis, meningitis.
  • Herpes simplex virus: Risk of disseminated infection, neonatal encephalitis, and high mortality without antiviral therapy.

Table 16. Ocular Complication Rates by Pathogen

Table 17. Long-Term Sequelae and Management Strategies

Key Points

Neisseria gonorrhoeae presents the most significant risk for severe corneal injury and systemic dissemination, often leading to complications such as ulceration, perforation, or sepsis. Chlamydia trachomatis and other bacterial pathogens tend to cause less aggressive disease but may still result in conjunctival scarring and chronic ocular issues when left untreated.

The timely administration of both topical and systemic antimicrobial therapy significantly reduces the likelihood of vision-threatening or life-threatening complications. Early therapeutic intervention remains the cornerstone of effective management.

Managing advanced or complicated cases often requires collaboration among multiple specialists. Ocular surgeons, pediatricians, infectious disease experts, and neurologists contribute essential perspectives to support recovery and mitigate systemic risks, particularly in cases involving gonococcal or herpetic infections.

Ongoing follow-up plays a critical role in the care of infants recovering from ophthalmia neonatorum. Periodic ophthalmologic evaluations help detect and address long-term complications, eg, glaucoma, corneal scarring, and refractive abnormalities, ensuring optimal visual development and minimizing permanent impairment. By understanding the full spectrum of potential complications and implementing preventive strategies, clinicians can preserve vision and overall health in neonates with ophthalmia neonatorum.