Ophthalmia neonatorum complicated with neonatal orbital cellulitis: A case series

Abstract Orbital cellulitis is an extremely rare but potentially lethal condition in neonates. The clinical presentation of neonatal orbital cellulitis can be non-specific, and minimal signs of periorbital inflammation may go unrecognised by inexperienced parents or primary care medical personnel, leading to delayed treatment. Herein, we present a case series describing ophthalmia neonatorum complicated with neonatal orbital cellulitis owing to delayed treatment. The clinical presentation, management and outcomes are described. One neonate had orbital cellulitis, while the other had impending orbital cellulitis, with both cases resulting from delayed treatment of ophthalmia neonatorum. Both neonates were hospitalised for systemic antibiotic treatment and fully recovered with good outcomes. Timely identification and treatment of ophthalmia neonatorum are critical to mitigate potential severe sequelae, such as neonatal orbital cellulitis.


Introduction
2][3] Its incidence varies widely across studies, which may be attributed to geographic and socioeconomic variations in di erent populations.][6] e infection may also spread from adjacent periorbital or facial infections, such as conjunctivitis, dacryocystitis, hordeolum, dental infection, direct inoculation from orbital trauma, animal or insect bite, ophthalmic surgery or periorbital skin infection. 6[4] Ophthalmia neonatorum is a form of conjunctivitis occurring in the neonatal period. 7Its incidence ranges from 1% to 17% depending on the socioeconomic characteristics of the region.For example, the rates vary from 1% to 2% in the United States and Europe and to 17% in Pakistan. 7,8However, ophthalmia neonatorum complicated with orbital cellulitis is extremely rare.We hereby report two cases of orbital cellulitis in neonates, which resulted from delayed referral and treatment of ophthalmia neonatorum.We hope that this case series serves as a reminder for primary care physicians to treat ophthalmia neonatorum as an ocular emergency and promptly refer cases to ophthalmologists upon the rst encounter with the condition.

Case presentation
Case 1 A full-term 14-day-old female neonate who was born via spontaneous delivery was referred from a polyclinic with a history of yellowish discharge from the left eye since day 9 of life.
e condition was followed by left eyelid swelling and erythema on day 13 of life, which were accompanied with inconsolable crying for one night.
e neonate remained active and tolerated feeding.Her mother was diagnosed with gestational diabetes mellitus under diet control and urinary tract infection (UTI) at 36 weeks of gestation.e neonate had a history of neonatal jaundice that did not require phototherapy.Her parents noticed her ocular problems and informed the medical o cer during the rst polyclinic follow-ups.However, the case was referred to an ophthalmologist only after the third visit to the polyclinic when the condition worsened.Upon receiving the referral, the ophthalmology team noticed that she was irritable during examination of her left eye.Ophthalmic examination of the left eye revealed an erythematous swollen eyelid with minimal yellowish discharge (Figure 1a).Pseudomembranes and associated meibomitis were noted (Figure 1b).e conjunctiva was severely injected and chemotic with subconjunctival haemorrhage.Furthermore, there was ophthalmoplegia at all gazes.Intravenous cefotaxime 50 mg/kg/dose QID for 14 days and oral azithromycin 20 mg/kg/ dose OD for 3 days were then administered.Guttae levo oxacin every 4 hour was added Nonetheless, the cornea was clear with a deep anterior chamber.
e pupillary re exes and fundus were normal.Right eye and systemic examinations showed unremarkable ndings, and the neonate was afebrile.A sample of her eye discharge was sent for swab culture and sensitivity test, revealing no growth of organisms.Computed tomography (CT) of the brain and orbit was performed, which showed left orbital cellulitis with no evidence of orbital collection or intracranial extension (Figure 2).as ancillary therapy.Frequent eye toileting and daily removal of pseudomembranes were performed together with adjunct preservativefree arti cial tear application, and low-dose guttae uorometholone was added 3 days later.e neonate responded well to antibiotic therapy, as evidenced by reduced redness and swelling of the eyelid and the ability to open her eyes without aid.Upon completion of intravenous antibiotic therapy for 14 days, there was neither redness nor swelling of the eyelid with remaining minimal chemosis and slightly injected conjunctiva (Figure 3a).She was discharged home with guttae levo oxacin QID, and her orbital cellulitis fully resolved by the rst week of follow-up (Figure 3b).

Case 2
A full-term 10-day-old male neonate born via spontaneous delivery was referred to the ophthalmology clinic for left upper eyelid redness since day 7 of life, accompanied with yellowish discharge.
e mother reported that she noted redness in his left eye since the rst day of life but did not seek medical attention at that time.e neonate remained active and tolerated feeding.His mother had vaginal candidiasis at 38 weeks of gestation, and treatment was given.
e neonate had neonatal jaundice that did not require phototherapy and was under polyclinic follow-up.Similar to case 1, the neonate's ocular problems were not alerted by healthcare personnel at the early onset of the disease until third visit to the polyclinic because of a worsening condition.e neonate became irascible upon examination of his left eye.His left eyelid was erythematous and swollen, accompanied with yellowish discharge.His conjunctiva was severely injected and chemotic with the presence of pseudomembranes (Figure 4a).Moreover, his extraocular movements were restricted at all gazes.Given the clinical signs suggesting orbital cellulitis, intravenous cefotaxime, oral azithromycin and guttae levo oxacin were administered.
e neonate responded well to treatment.His eyelid swelling and redness along with chemosis resolved more rapidly than did those of case 1 (Figure 4b).e neonate was discharged after completing 7 days of intravenous antibiotic treatment.He was prescribed with syrup cefuroxime 15 mg/ kg/dose BD and guttae levo oxacin for 1 week upon discharge.He fully recovered after the 2-week course of treatment (Figure 4c).

Discussion
e prevalence of bacterial ora varies across di erent age groups owing to di erences in their immunity and anatomical structures. 9][10] Conversely, Haemophilus species may be more common in older infants. 9Serratia species are occasionally recognised as a cause of hospital-acquired infection such as UTI, respiratory tract infection or wound infection. 11In this study, S. marcescens was cultured in case 2.
In the present cases, the infection may have started from vertical transmission from the mothers who had a history of UTI and vaginal candidiasis, leading to perinatal infection and, subsequently, ophthalmia neonatorum. 12ater, the delayed treatment of ophthalmia neonatorum may have contributed to the development of orbital cellulitis.A study conducted in Ilorin found that antenatal maternal vaginal discharge is also one of the predisposing factors of ophthalmia neonatorum. 12clinical presentation of neonatal orbital cellulitis can be non-speci c, which makes it challenging to diagnose.Simple fever, reduced milk intake, moaning or inconsolable crying, minimal eye discharge or mild conjunctival redness may present as the initial symptoms along with non-obvious periorbital swelling or erythema.2 If the minimal signs of periorbital in ammation are not recognised by inexperienced medical personnel in primary care settings, treatment may be delayed.2 us, it is crucial for primary care medical personnel to have a high level of suspicion and be aware of potential ocular problems, especially when informed by caretakers.Delayed treatment can lead to serious complications, as demonstrated in the present cases.
Malays Fam Physician 2024;19:5 Ceftriaxone is commonly used as the rstline antibiotic for orbital cellulitis in patients of other ages.In the present cases, cefotaxime was administered, since ceftriaxone carries a higher risk of hyperbilirubinaemia in neonates if more than one dose is needed in the short term. 13,14Both ceftriaxone and cefotaxime are broad-spectrum antibiotics that cover a wide range of bacteria, including Streptococcus and Staphylococcus species, which are the most common causative organisms. 15ncurrently, we highly recommend regular eye toileting and frequent preservative-free arti cial tear application as adjunctive therapy to locally remove the causative pathogen. 7aily removal of pseudomembranes is proven to be helpful in accelerating the healing of the in ammatory state of conjunctivitis.Furthermore, low-dose topical steroids can add an adjuvant e ect to shorten the recovery period by reducing in ammation. 16rly detection and prompt treatment are crucial for a favourable outcome of neonatal orbital cellulitis.In less severe cases, a shorter period of hospitalisation and faster recovery can be expected, as demonstrated in case 2. However, in severe cases, such as those with abscess formation or associated sepsis, a longer period of hospitalisation and more aggressive treatment such as surgical drainage may be required. 1,5,6,17,18imary care teams play a crucial role in managing cases of ophthalmia neonatorum.Any instances of ophthalmia neonatorum, including eyelid swelling or redness, should be promptly referred to an ophthalmologist for thorough assessment and evaluation.It is important for primary care teams to be aware that ophthalmia neonatorum is an ocular emergency requiring immediate referral. 19imary care team members, especially junior medical o cers, are strongly encouraged to attend the 'Primary Eye Care Course' to enhance their foundational knowledge of basic eye care in primary care settings.

What is the implication to patients?
Our report emphasises the signi cance of raising awareness among primary care medical personnel and parents about the need for prompt recognition and management of ophthalmia neonatorum to achieve optimal outcomes for neonates.e initial symptoms of ophthalmia neonatorum such as eye discharge or conjunctival redness should be taken seriously, and neonates must be referred to an ophthalmologist to start antibiotic eyedrop treatment to prevent progression to serious conditions such as orbital cellulitis.

Figure 2 .
Figure 2. Computed tomography scan of the brain and orbit showing left periorbital subcutaneous fat stranding and thickening [*] with thickened left orbital septum and superior and inferior tarsal muscles.

Figure 3 .
Figure 3. (a) Resolved left erythematous swollen eyelid with remaining minimal chemosis and slightly injected conjunctiva.(b) Fully recovered left orbital cellulitis with no chemosis or injection of the conjunctiva.

Figure 4 .
Figure 4. (a) Left severely injected conjunctiva with 360-degree chemosis and yellowish purulent discharge.(b) Resolving left conjunctival injection and chemosis after 7 days of treatment.(c) Fully recovered cellulitis with no chemosis or injection of the conjunctiva.Consequently, CT of the brain and orbit was performed, which revealed left-enhancing periorbital soft tissue swelling representing periorbital cellulitis with no evidence of orbital collection or intracranial extension (Figure5).Left eye swab culture and sensitivity test demonstrated the growth of Serratia marcescens.

Figure 5 .
Figure 5. Computed tomography scan of the brain and orbit showing left periorbital soft tissue swelling with no fat stranding [+] representing left periorbital cellulitis.