European Journal of Cardiovascular Medicine

Ophthalmia neonatorum (ON) is conjunctival inflammation occurring within the first 28 days of life and ranges clinically from mild mucopurulent discharge to hyperacute keratoconjunctivitis with corneal ulceration, perforation, sepsis and permanent visual loss. Classically, Neisseria gonorrhoeae presents early (2–5 days), Chlamydia trachomatis later (5–12 days), and other bacteria (for example Staphylococcus spp., Streptococcus spp., Gram-negative bacilli) as well as herpes simplex virus can present across this window; systemic associations (notably chlamydial pneumonitis at 1–3 months) underline that ON is not merely a local eye disease but part of a broader perinatal infectious spectrum [1, 2].

Despite long-standing prevention programs, ON persists worldwide with heterogeneous incidence and shifting etiologies. A recent systematic review and meta-analysis (2000–2023 data) found wide variability in burden across regions, frequent isolation of non-STI organisms (particularly Staphylococcus spp.), and notable antimicrobial resistance (AMR) patterns among ocular isolates, underscoring the need for contemporary, locale-specific data to inform care pathways [3].

Prevention has historically relied on universal postnatal ocular prophylaxis plus antenatal screening. The US Preventive Services Task Force (USPSTF) re-affirmed an “A” recommendation for prophylactic erythromycin ointment for all newborns because even rare missed maternal infections can lead to rapidly blinding gonococcal disease; CDC guidance similarly stresses prophylaxis alongside maternal screening and timely treatment [4]. However, evidence comparing agents is mixed and mostly older; the Cochrane review highlights moderate- to low-certainty findings across trials spanning many decades, while a landmark randomized trial suggested 2.5% povidone-iodine reduced infectious conjunctivitis (especially chlamydial) with less chemical irritation versus silver nitrate or erythromycin though povidone-iodine is not universally approved/standardized for this indication [5]. Policies also differ internationally: several European countries have replaced universal prophylaxis with enhanced antenatal screening, whereas most US states still mandate universal prophylaxis, reflecting ongoing debate about optimal prevention strategies in different epidemiologic contexts [4].

Concurrently, global AMR trends complicate management: N. gonorrhoeae is a WHO-listed priority pathogen with rapidly evolving resistance that has narrowed effective systemic options and raises concern about future treatment failures; local ocular microbiology also shows resistance among common neonatal isolates [6]. Recent prospective work from Ghana found Staphylococcus spp. predominated, no gonococcal cases were isolated, and high tetracycline resistance was observed implicating postnatal acquisition and environmental/maternal factors; Indian hospital-based cohorts similarly report staphylococcal predominance and identify perinatal risk factors such as premature rupture of membranes and midwife/unclean delivery practices [7]. Together, these patterns suggest ON’s etiologic mix and resistance profile are dynamic, geographically specific, and influenced by obstetric care quality, prophylaxis practices, and community STI prevalence [8]. Many available studies are retrospective or predate current STI epidemiology and AMR trends; prospective data linking the full clinical spectrum (from mild conjunctivitis to vision-threatening disease) with culture-confirmed/NAAT-confirmed etiologies, antimicrobial susceptibility, maternal/perinatal risk factors, time-to-presentation, and short-term outcomes (need for admission, corneal involvement, treatment failure, recurrence) are limited particularly from low- and middle-income settings and large public hospitals. Evidence informing the real-world impact of universal prophylaxis versus risk-based strategies on clinical outcomes in contemporary settings is also scarce, and standardization of outcome definitions is inconsistent [9, 10].  Aim of the study was to prospectively characterize the clinical spectrum and short-term outcomes of ophthalmia neonatorum in our center; determine etiologic agents using culture and antimicrobial susceptibility patterns; and identify maternal, perinatal and care-pathway factors associated with severe disease and adverse outcomes, thereby informing locally relevant prevention and treatment strategies.

This was a prospective observational study conducted jointly by the Departments of Ophthalmology and Pediatrics, Mamata Medical College and General Hospital, Khammam, Telangana, India. Consecutive neonates presenting with conjunctivitis were included. The study was carried out over a period of 12 months. A total of 100 neonates aged ≤28 days with clinical features of conjunctivitis were enrolled. The sample size was based on the expected case load over the study period.

Eligibility Criteria

• Inclusion: neonates ≤28 days of age presenting with redness, conjunctival discharge, eyelid swelling, or chemosis, with parental consent.
• Exclusion: neonates already on topical/systemic antibiotics for >48 hours, those with congenital ocular anomalies, or critically ill neonates in whom ocular examination/sampling was not feasible.

Clinical Evaluation

Detailed history was recorded, including: birth details (mode and place of delivery, gestational age, birth weight), maternal antenatal history (screening/treatment for infections), and perinatal risk factors (premature rupture of membranes, prolonged labor, instrumentation).
A complete ocular examination was performed noting:

• Laterality, type of discharge, conjunctival congestion, eyelid edema
• Presence of membranes, corneal involvement, or anterior chamber reaction.
  Systemic examination was done by Pediatrics to look for fever, respiratory symptoms, or signs of sepsis.

Microbiological Methods

Conjunctival swabs were collected under aseptic precautions before starting any treatment:

• Direct Microscopy: one swab was used for Gram stain to identify pus cells and bacterial morphology.
• Culture: another swab was inoculated onto 5% sheep blood agar, MacConkey agar, and chocolate agar plates. For suspected Neisseria gonorrhoeae, Modified Thayer–Martin medium with CO₂ incubation was used.
• Identification and Susceptibility: bacterial isolates were identified by standard biochemical tests. Antimicrobial susceptibility testing was performed using the Kirby–Bauer disk diffusion method according to Clinical and Laboratory Standards Institute (CLSI) guidelines.

Management Protocol

All neonates received empirical topical antibiotic treatment as per hospital protocol immediately after sample collection. Cases with severe infection (hyperacute conjunctivitis, corneal involvement, systemic illness) were admitted and managed with systemic antibiotics as required. Treatment was modified based on culture and sensitivity reports.

Follow-Up

Neonates were followed up at 48–72 hours, at 7 days, and at 14 days after initiation of treatment. At each visit, ocular signs were reassessed and outcomes noted, including clinical improvement, persistence or worsening need for admission, and recurrence.

Outcomes Measured

• Clinical spectrum at presentation
• Bacterial isolates and their antimicrobial susceptibility
• Short-term outcomes: resolution, complications (corneal involvement, recurrence), and treatment failure
• Association of maternal and perinatal factors with severe outcomes

Ethical Considerations

The study was approved by the Institutional Ethics Committee of Mamata Medical College and General Hospital, Khammam. Written informed consent was obtained from parents or guardians before enrolment.

Statistical Analysis

Data were entered in a structured proforma and analyzed using SPSS version 25.0. Continuous variables were summarized as mean ± SD or median (IQR). Categorical variables were presented as proportions. Associations were tested using chi-square/Fisher’s exact test for categorical variables and t-test/Mann–Whitney U test for continuous variables. A p value <0.05 was considered statistically significant.

Table 1: Birth details of neonates with ophthalmia neonatorum (n = 100)

Table 1 summarizes the birth details of the 100 neonates with ophthalmia neonatorum. A majority were delivered by normal vaginal delivery (62%), with 38% born by cesarean section. Most neonates were delivered in institutional settings (84%), while 16% were home births. Preterm births (<37 weeks) accounted for 28% of cases, with a mean gestational age of 36.1 ± 2.4 weeks, while term neonates had a mean gestational age of 38.4 ± 1.2 weeks. Low birth weight (<2.5 kg) was observed in 22% of infants (mean 2.38 ± 0.42 kg), whereas 78% had normal birth weight (mean 3.01 ± 0.36 kg). These findings indicate that although most cases occurred among term, normal-weight neonates delivered in hospital settings, a considerable proportion of preterm, low-birth-weight, and home-delivered infants were also affected, suggesting their increased vulnerability.

Figure 1: Maternal antenatal history and perinatal risk factors in neonates with ophthalmia neonatorum (n = 100)

Figure 1 presents the maternal antenatal history and perinatal risk factors among the study cohort. Most mothers (72%) had adequate antenatal screening for major infections, while 28% had inadequate or no screening. A history of genital or urinary tract infection during pregnancy was noted in 18% of mothers, though only two-thirds of them received treatment. Premature rupture of membranes (PROM) was observed in 20% of deliveries, and prolonged labor in 15%. Instrumental delivery with forceps or vacuum was recorded in 10% of cases. These findings highlight that, although the majority of mothers received standard antenatal care and delivered without complications, a substantial proportion had identifiable risk factors—particularly inadequate screening, maternal infections, and PROM—that could contribute to the occurrence and severity of ophthalmia neonatorum.

Table 2: Ocular examination findings in neonates with ophthalmia neonatorum (n = 100)

Table 2 summarizes the ocular examination findings of the neonates with ophthalmia neonatorum. Unilateral involvement was more common (58%) than bilateral disease (42%). Mucopurulent discharge was the predominant presentation (65%), followed by purulent discharge (20%) and watery discharge (15%). Conjunctival congestion was observed in almost all cases, most often of moderate grade (44%), with 38% mild and 18% severe with chemosis. Eyelid edema was absent in about one-third (34%) of neonates, while 40% had mild swelling and 26% had moderate to severe edema. These findings indicate that most infants presented with moderate ocular inflammation characterized by mucopurulent discharge, conjunctival congestion, and variable lid swelling.

Table 3: Ocular examination findings in neonates with ophthalmia neonatorum (n = 100)

Table 3 shows the ocular features of neonates with ophthalmia neonatorum. Unilateral disease was slightly more frequent (58%) than bilateral involvement (42%). Mucopurulent discharge was the most common presentation (65%), with purulent profuse discharge in 20% and watery discharge in 15%. Conjunctival congestion was observed in all cases, predominantly moderate (44%), followed by mild (38%) and severe with chemosis (18%). Eyelid edema was present in two-thirds of neonates, with 40% mild and 26% moderate to severe, while 34% had no edema. Membranes or pseudomembranes were noted in 12% of cases, corneal involvement in 8%, and anterior chamber reaction in 3%.

Table 4. Systemic examination findings in neonates with ophthalmia neonatorum (n = 100)

Table 4 outlines the systemic examination findings among the study cohort. Fever was present in 14% of neonates, while 10% exhibited respiratory symptoms such as cough, tachypnea, or chest retractions. Signs of sepsis, including poor feeding, lethargy, and temperature instability, were observed in 6% of cases. Skin or mucosal lesions suggestive of herpes simplex infection or bacterial sepsis were recorded in 3% of neonates. These results show that although most infants presented with localized ocular disease, a minority demonstrated systemic involvement, underlining the need for careful pediatric evaluation to detect and manage potentially serious complications.

Table 5: Antimicrobial susceptibility pattern of major isolates (% sensitive)

Table 5 presents the antimicrobial susceptibility profile of the major bacterial isolates. Among Staphylococcus aureus isolates, sensitivity was highest to ceftriaxone (100%) and ciprofloxacin (90%), while moderate resistance was noted to erythromycin (32%). Coagulase-negative staphylococci (CONS) showed a similar pattern, with full sensitivity to ceftriaxone, high susceptibility to ciprofloxacin (85%), and lower sensitivity to erythromycin (61%). Streptococcus pneumoniae isolates were fully sensitive to ceftriaxone and showed 88% sensitivity to ciprofloxacin and 75% to erythromycin. Gram-negative bacilli (Klebsiella pneumoniae and E. coli) displayed full sensitivity to ceftriaxone, good susceptibility to ciprofloxacin (83% and 80%, respectively), but lower rates to erythromycin (50% and 40%). Pseudomonas aeruginosa isolates were uniformly sensitive to ciprofloxacin and ceftriaxone, while Neisseria gonorrhoeae showed 100% sensitivity to both agents tested. Overall, ceftriaxone and ciprofloxacin were the most effective antibiotics, whereas resistance to erythromycin was commonly observed across isolates.

Table 6: Follow-up outcomes of neonates with ophthalmia neonatorum (n = 100)

Table 6 outlines the follow-up outcomes of neonates with ophthalmia neonatorum. At 48–72 hours, 62% of infants showed clinical improvement, while 30% had persistent signs, and 5% worsened; 8% required admission for systemic therapy, and 3% were lost to follow-up. By 7 days, the majority (85%) had improved, only 10% continued to have residual conjunctivitis, and 2% worsened; recurrence was noted in 3% of cases. At 14 days, 94% of neonates had complete resolution, while persistence was seen in only 3% and recurrence in 2%; just one case showed progressive worsening. These results highlight that with timely and appropriate management, most cases of ophthalmia neonatorum resolve within two weeks, with only a small proportion developing complications or requiring hospital admission.

Table 7: Association of maternal and perinatal factors with severe outcomes in ophthalmia neonatorum (n = 100)

*Statistically significant (p<0.05)

Table 7 depicts the association of maternal and perinatal factors with severe outcomes in ophthalmia neonatorum. Severe outcomes were significantly more frequent among neonates whose mothers had inadequate or no antenatal screening (28.6% vs 8.3%, p=0.04), a history of untreated maternal infection during pregnancy (33.3% vs 9.8%, p=0.01), and in cases with premature rupture of membranes (30% vs 10%, p=0.02). Prolonged labor (>18 hours) and instrumental delivery were also associated with higher proportions of severe cases (26.7% and 30%, respectively) compared with their counterparts, though these did not reach statistical significance. These findings highlight that preventable maternal and perinatal factors particularly inadequate antenatal care, maternal infection, and PROM play a critical role in determining the severity of ophthalmia neonatorum.

In this prospective study of 100 neonates with ophthalmia neonatorum (ON), most infants presented with mucopurulent discharge, conjunctival congestion, and varying degrees of lid edema. Severe findings such as membranes (12%), corneal involvement (8%), and anterior chamber reaction (3%) were relatively uncommon. Culture positivity was 76%, with Staphylococcus aureus as the predominant isolate, followed by coagulase-negative staphylococci and Gram-negative bacilli. These findings are consistent with recent cohorts in which staphylococcal species are the leading pathogens in ON [11].

Our results align with the Ghanaian prospective study by Boadi-Kusi et al., which reported culture positivity in 52.4% of neonates, with Staphylococcus spp. predominating and no cases of Neisseria gonorrhoeae isolated [7]. Similarly, Indian studies have consistently shown staphylococci to be the commonest isolates, though proportions vary between S. aureus and coagulase-negative staphylococci [12]. Wadhwani et al. emphasized the role of maternal and perinatal risk factors such as premature rupture of membranes (PROM) and midwife manipulation in transmission [8]. Our study likewise demonstrated significant associations between severe outcomes and PROM, inadequate antenatal screening, and untreated maternal infections.

The low isolation rate of N. gonorrhoeae (2%) in this study is comparable to contemporary data from both Africa and India, where gonococcal ophthalmia has become relatively rare [13]. Nonetheless, vigilance remains crucial because gonococcal conjunctivitis can lead to corneal perforation and blindness if untreated. International guidelines continue to recommend universal ocular prophylaxis to prevent gonococcal ON, with the U.S. Preventive Services Task Force reaffirming this as an “A” grade recommendation [14]. CDC guidance also stresses that suspected or confirmed gonococcal ON requires systemic treatment, as topical therapy alone is inadequate [15]. With N. gonorrhoeae now listed as a WHO priority pathogen due to rising antimicrobial resistance [16], surveillance and preparedness are essential even in settings where incidence is low.

Clinical outcomes in our study were favorable: by day 7, 85% of neonates showed significant improvement, and by day 14, 94% had complete resolution. Only 8% required admission, mainly for hyperacute or systemic illness, and recurrences were rare (2%). These figures are similar to those reported in earlier Indian and African studies, where most cases resolve with prompt, culture-guided topical therapy and systemic treatment reserved for severe cases [17].

Strengths of our study include the prospective design, multidisciplinary evaluation, and scheduled follow-up. Limitations include the single-center setting and the use of only microscopy and culture, which may under-detect Chlamydia trachomatis. Prior Indian work, such as Mohile et al., has shown that C. trachomatis can account for a notable fraction of neonatal conjunctivitis [18]. Despite this limitation, our culture-based results reflect real-world diagnostic practice in many resource-limited centers

This prospective study from Mamata Medical College demonstrated that staphylococcal species remain the leading causes of ophthalmia neonatorum, with Gram-negative bacilli contributing less frequently and gonococcal infection being rare. Most neonates responded well to early, culture-guided topical therapy, while severe outcomes were concentrated in infants with identifiable perinatal risk factors such as PROM, maternal infection, and inadequate antenatal screening. These findings reinforce the importance of strengthening peripartum preventive strategies including universal ocular prophylaxis, antenatal infection screening, and safe delivery practices while maintaining culture-based surveillance and susceptibility monitoring to guide empiric therapy and reduce complications.

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