Ophthalmia neonatorum is a type of conjunctivitis that occurs in the neonatal period, affecting 1% to 12% of neonates (see  Ophthalmia Neonatorum). This condition commonly gets transmitted during vaginal delivery, and it correlates with severe complications (eg, corneal ulceration and perforation), which can potentially result in permanent blindness. Due to the significant morbidity associated with this disease, the United States Preventive Services Task Force (USPSTF) has issued new guidelines regarding antibiotic use in all newborns to prevent ophthalmia neonatorum. These guidelines were established to prevent the vertical transmission of gonococcal infection, which can occur in up to 50% of cases when prophylaxis is not administered. In 2010, The Centers for Disease Control and Prevention (CDC) developed the guidelines for the management of sexually transmitted infections (STIs), in which prophylaxis with erythromycin ointment (0.5%) or azithromycin solution 1% (if erythromycin not available) is recommended as a part of the routine newborn care for ophthalmia neonatorum prevention, considering that is effective and inexpensive. In these guidelines, routine screening and appropriate treatment, including for the partners of all pregnant women during the first trimester, are also recommended. During the third trimester, screening follow-up for those women considered high risk (eg, multiple sex partners and individuals aged 24 years or younger) is advisable. Silver nitrate effectively prevents gonococcal ophthalmia neonatorum; however, its use has been discontinued due to the high risk of developing chemical conjunctivitis in approximately 50% of the cases. Ophthalmia neonatorum, also known as neonatal conjunctivitis, is a severe form of conjunctival inflammation occurring within the first month of life. This condition represents a significant cause of neonatal ocular morbidity worldwide and, if not promptly recognized and treated, can lead to corneal ulceration, scarring, and permanent visual impairment. Historically, ophthalmia neonatorum was most commonly associated with infection, but in modern practice, a broader spectrum of bacterial, viral, and chemical etiologies is recognized. Early identification and management are therefore critical to prevent complications that can have lifelong consequences. The incidence of ophthalmia neonatorum varies geographically, reflecting differences in maternal infection rates, availability of prenatal care, and adherence to prophylactic protocols. In high-resource settings, the incidence has declined markedly following the implementation of universal ocular prophylaxis—most commonly topical erythromycin ointment applied shortly after birth—and routine screening and treatment of maternal STIs during pregnancy. However, in low- and middle-income countries, limited access to prenatal screening and inconsistent application of prophylaxis contribute to higher rates of neonatal conjunctivitis. Recent epidemiological surveys estimate incidence rates ranging from <1% in well-resourced maternity services to >10% in underserved regions. Etiologically, ophthalmia neonatorum is classified according to the causative agent and the timing of onset. Early-onset cases (within 24–48 hours of birth) often result from chemical irritants, such as silver nitrate or povidone-iodine drops used for prophylaxis, or from viruses vertically transmitted in utero (notably herpes simplex virus). Bacterial causes, which may manifest between days 2 and 7 of life, include , and . Gonococcal conjunctivitis typically presents most aggressively, with copious purulent discharge, eyelid edema, and rapid progression to corneal involvement if untreated. Chlamydial conjunctivitis, in contrast, tends to have a more indolent course with watery or mucopurulent discharge emerging around day 5 to 14, often accompanied by nasopharyngeal colonization and potential otitis media. Viral etiologies, particularly herpes simplex virus type 2, may present later (days 7–14) with conjunctivitis often accompanied by systemic signs, eg, fever, irritability, and vesicular skin lesions. The pathophysiology of ophthalmia neonatorum centers on the immature anatomy and immunology of the newborn eye. The neonatal conjunctiva and cornea exhibit increased permeability, and tear film production is limited, thereby reducing the natural clearance of pathogens. In addition, maternal antibodies—while providing some passive immunity—may not fully protect against pathogens acquired during passage through the birth canal. For , bacterial adherence to conjunctival epithelial cells triggers a robust inflammatory response, characterized by the infiltration of polymorphonuclear leukocytes and the release of proteolytic enzymes that can damage the corneal stroma. Chlamydia induces a less fulminant but chronic inflammatory milieu that can lead to conjunctival scarring if untreated. Viral replication in epithelial cells contributes to cytopathic effects and secondary bacterial superinfection. Clinically, the diagnosis of ophthalmia neonatorum requires a high index of suspicion. Infants present with varying degrees of eyelid swelling, conjunctival redness, and ocular discharge. The nature of the discharge—watery, mucopurulent, or frankly purulent—guides the differential. Gonococcal infection is suspected when heavy purulence appears as early as 2 to 3 days of life; chlamydial infection should be considered with milder, delayed-onset discharge. Chemical conjunctivitis typically develops within hours of prophylactic instillation and resolves within 24 to 48 hours without the need for specific antimicrobial therapy. The presence of eyelid vesicles or systemic signs may distinguish viral conjunctivitis. A thorough history—particularly of maternal STI status, duration of membrane rupture, and prophylactic measures administered at birth—is essential. Laboratory confirmation involves gram staining and culture of conjunctival scrapings for gonorrhea, as well as nucleic acid amplification tests (NAATs) for chlamydia and gonococcus. Additionally, viral culture or polymerase chain reaction (PCR) is used for the herpes simplex virus. Management of ophthalmia neonatorum hinges on prompt, appropriate antimicrobial therapy tailored to the suspected or confirmed pathogen. For gonococcal conjunctivitis, systemic antibiotic therapy is mandatory—typically a single intramuscular dose of ceftriaxone, accompanied by saline eyelid cleansing and topical antibiotic drops to reduce surface bacterial load. Chlamydial conjunctivitis is treated with oral erythromycin or azithromycin, which reach therapeutic concentrations in tears and reduce the risk of nasopharyngeal and ear involvement. Chemical conjunctivitis typically requires only supportive care, including lubrication of the affected area. In suspected neonatal herpes infection, systemic acyclovir should be initiated urgently, given the risk of disseminated disease. Close ophthalmologic follow-up is necessary to monitor for corneal complications. Any sign of corneal ulceration or scarring requires intensive management, possibly including topical antibiotics, antiviral agents, or surgical intervention in severe cases. Prevention of ophthalmia neonatorum is equally paramount. Universal ocular prophylaxis remains a cornerstone of newborn care, with current guidelines favoring the application of erythromycin 0.5% ointment within 1 hour of birth. Some settings have adopted povidone-iodine as an alternative, given concerns about erythromycin resistance and availability. However, prophylaxis does not obviate the need for maternal STI screening and treatment: prenatal testing for and , and treatment of positive cases, substantially reduces neonatal infection risk. Education of expectant mothers about safe sexual practices, diligent prenatal care, and early recognition of symptoms in neonates further enhances prevention efforts. Ophthalmia neonatorum poses a significant public health challenge, spanning the domains of obstetrics, neonatology, infectious diseases, and ophthalmology. Effective control requires an integrated approach, ensuring access to prenatal screening and treatment, guaranteeing the consistent application of ocular prophylaxis at birth, educating healthcare practitioners and parents about the early signs of infection, and establishing protocols for rapid diagnosis and treatment. In resource-limited settings, strengthening healthcare infrastructure, eg, supply chains for prophylactic agents, laboratory capacity for NAAT testing, and training of primary care clinicians, can markedly reduce the burden of neonatal conjunctivitis and its sequelae. Despite advances, challenges remain. Antimicrobial resistance among gonococcal strains poses a threat to undermine current treatment regimens, necessitating ongoing surveillance and potential adjustments to treatment regimens. The emergence of new enteric and respiratory pathogens capable of causing neonatal conjunctivitis underscores the need for vigilant epidemiological monitoring. Ultimately, disparities in healthcare access persist, driving uneven outcomes worldwide. Achieving universal coverage of prenatal STI screening and ocular prophylaxis, coupled with timely therapeutic interventions, is essential to safeguarding the vision and health of newborns worldwide. Ophthalmia neonatorum is a preventable and treatable condition whose successful management hinges on interprofessional collaboration, adherence to evidence-based guidelines, and equitable access to healthcare resources. By integrating robust preventive strategies with prompt, pathogen-specific treatments, clinicians can virtually eliminate the risk of vision-threatening complications in this vulnerable population, fulfilling the promise of modern neonatal care and preserving the gift of sight from the very first days of life.