Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

OBJECTIVE: To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3 weeks off regimen. RESULTS: Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52 years; range, 11-87 years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6 months (median, 5 months; range, 1-36 months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). CONCLUSION: Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Ocular surface squamous neoplasia with orbital tumour extension: risk factors and outcomes.

PURPOSE: To describe the risk factors, clinical features, histopathology, treatment, and outcomes of patients with orbital tumour extension of ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study of 51 patients with orbital tumour extension (cases) and 360 patients without orbital extension (controls). RESULTS: Of 1,653 patients with OSSN, orbital tumour extension was noted in 51 (3%) cases. The risk factors for orbital tumour extension included outdoor occupation (p < 0.03; Odds ratio (OR) = 1.96), Human Immunodeficiency Virus (HIV) infection (p < 0.0001; OR = 5.81), prolonged duration of symptoms (p = 0.01; OR = 1.02), tumour bilaterality (p = 0.02; OR = 2.92), forniceal and tarsal conjunctival involvement, diffuse tumour (p < 0.0001; OR = 9.13), inferior quadrantic location (p < 0.0001; OR = 7.51), increased tumour thickness (p = 0.04; OR = 1.59), higher % of ocular surface involvement (p = 0.002; OR = 1.12), nodular (p = 0.002; OR = 2.61) and nodulo-ulcerative (p < 0.0001; OR = 11.05) tumour morphology, poorly differentiated tumours (p = 0.006; OR = 4.23); invasive squamous cell carcinoma (SCC) (p < 0.0001; OR = 29.76), spindle cell and mucoepidermoid variant (p = 0.02; OR = 16.94) tumours. At a mean follow-up period of 27 months, tumour recurrence in the socket was noted in 1 (2%), locoregional lymph node metastasis (LNM) in 15 (29%) patients, and nine (18%) patients died due to systemic metastasis (SM). T4 tumour at presentation was a risk factor for LNM (p = 0.01; Hazard ratio (HR) = 5.60) and SM (p = 0.0003; HR = 5.09). CONCLUSION: Orbital extension of OSSN is rare. Outdoor occupation, HIV infection, larger and thicker tumours in the inferior quadrant with forniceal and/or tarsal conjunctival involvement with nodular or noduloulcerative morphology, poor tumour differentiation, SCC, spindle cell and mucoepidermoid variants on histopathology are at increased risk for orbital tumour extension.

Microbiology Profile of COVID-19-Associated Rhino-Orbital Mucormycosis Pathogens in South India.

This study describes the microbiological and histopathological features of patients with COVID-19-associated rhino-orbital mucormycosis (ROM) seen at the L V Prasad Eye Institute between May and August 2021. Diagnosed clinically and radiologically, 24 patients with ROM were included in the study. Deep nasal swabs or endoscopically collected nasal swabs or orbital tissues were submitted for microbiological evaluation and in vitro susceptibility testing by microbroth dilution for natamycin, amphotericin B, caspofungin, posaconazole, ketoconazole, and voriconazole. Cultures were processed by 28S ribosomal DNA polymerase chain reaction and molecular sequencing. A portion of orbital tissues was also sent for histopathological evaluation. The age of the patients ranged from 27 to 75 (mean 48.58 ± 14.09) years and the majority (79%) were male. Nineteen patients were known to be diabetic prior to developing ROM and 18 patients had recovered from active COVID-19 infection. Thirteen patients had a history of hospitalization during COVID-19 infection and eight received steroids. Of the 24 samples, microbiological evaluation identified Rhizopus arrhizus in 12, Rhizopus microsporus in 9, Lichtheimia ramosa in 2, and Rhizopus delemar in 1. Twelve isolates were tested for antifungal susceptibility and all were susceptible to natamycin and amphotericin B. The susceptibility to posaconazole was high, with minimum inhibitory concentration (MIC) < 2 µg/mL for 10/12 (84%) isolates, whereas the MIC of other drugs varied. Histopathological examination of tissues showed acute fulminant disease, granuloma formation, and vascular invasion by the fungal pathogens in these specimens. Rhizopus arrhizus was predominantly associated with ROM and most isolates were susceptible to amphotericin B and posaconazole. Further studies are needed to corroborate the findings and explain possible underlying links.

Molecular diagnosis of rhino-orbital mucormycosis in a COVID-19 setting.

PURPOSE: Mucormycosis is a severe fungal infection caused by species of the order Mucorales. Early and accurate diagnosis is a prerequisite in the management of the disease. In the present study, we evaluated and compared two PCR-based techniques for the diagnosis and identification of mucormycosis in patients with rhino-orbital mucormycosis (ROM) post-COVID-19. METHODS: Diagnosed clinically and radiologically, 25 patients of ROM were included in the study and endoscopically or blind collected nasal swabs or orbital tissues were submitted for microbiological evaluation (direct microscopy + culture) and PCR using primers targeting two different loci (ITS and 28S rDNA region) for diagnosis. All PCR products were further processed for species identification using Sanger sequencing whenever possible. RESULT: Of the 25 samples included in the study, 16 samples were positive for presence of fungal filaments by Smear suggestive of Mucorales sp., but only 7/25 grew in culture. ITS-based PCR was able to identify mucormycosis in 7/25 (28%) samples and 28S rDNA PCR showed positivity for 19/25 (76%) samples. Rhizopus oryzae was found to be the predominant species in our study. The sensitivity and specificity of 28S rDNA PCR compared to culture were found to be 85.71% and 27.78%, respectively, while for ITS-based PCR, they were 42.86% and 77.78%, respectively. CONCLUSIONS: 28S rDNA-based PCR is a reliable and sensitive method for early diagnosis of mucormycosis. Molecular techniques have shown a promising future to provide quick and effective treatment by accurately identifying the aetiologic agent.

Neurotization of the human cornea - A comprehensive review and an interim report.

We present a comprehensive review of existing literature on surgical corneal neurotization (SCN) as a treatment modality for neurotrophic keratopathy (NK) with an interim report of seven cases where SCN was performed using the indirect approach and followed up till 18 months postoperatively to look for improvement in ocular surface, corneal sensations, and nerve regeneration by using in vivo confocal microscopy (IVCM). A literature search was performed for publications with keywords "corneal nerves," "neurotization," "esthesiometry," "corneal anesthesia," and "neurotrophic keratopathy." All literature available till December 31, 2020 was reviewed and included to describe NK and its management options, particularly SCN. NK is associated with absent or reduced corneal sensations and is managed using a step-ladder algorithm ranging from medical management for symptomatic relief to surgical corneal neurotization. Both direct and indirect approaches of SCN have a favorable outcome with reduced surgical morbidity in the indirect approach using sural nerve graft. Post neurotization, corneal sensation recovery may take up to 3-6 months, while nerve regeneration on confocal microscopy can take as long as 6 months-1 year.

Long term outcomes of transcutaneous non-image guided bleomycin sclerotherapy in orbital/adnexal lymphatic malformations: a protocol-based management in 69 eyes.

OBJECTIVES: To study the efficacy and the long-term outcomes of treating micro and macrocystic orbital and/or adnexal lymphatic malformations (OA-LM) with protocol-based bleomycin sclerotherapy. METHODS: A retrospective interventional study of 69 eyes having OA-LM treated with non-image guided transcutaneous or transconjunctival bleomycin sclerotherapy (1IU/ml aqueous solution) between December 2014 and December 2018. Based on clinical regression, the outcomes were classified as excellent, good, fair and poor. RESULTS: The mean age at presentation was 20 ± 16 years (median 16; range 1 month to 70 years). The orbital-palpebral variant was the most common presentation, seen in 29 patients (42%). Microcystic morphology was seen in 34(49%), macrocystic in 22 (32%) and mixed cyst in 13 (19%) patients. Mean units of bleomycin injected per patient were 9 ± 8 IU (median 5.5 IU, range 1-38 IU). Mean number of treatment sessions required were 2 ± 1 (median 2, range 1-6). The response was excellent in 43 (62%), good in 12 (17%), fair in 9 (13%) and poor in 5 (7%) patients. These responses were comparable across the morphological subgroups (p = 0.24, chi-square test). Adverse reactions noted were inflammation in 11 eyes (16%) and peri-ocular pigmentation in 15 (22%). There was a sustained tumour regression over a mean follow-up duration of 3.5 years (median 3; range 1.5-5 years). CONCLUSIONS: Seventy-nine percent of eyes with OA-LM showed a good outcome with transcutaneous and/or transconjunctival non-image guided bleomycin sclerotherapy with no serious adverse events. The results were promising over long-term follow-up.

Ocular Surface Squamous Neoplasia With Coexistent Microbial Keratitis: Incidence, Risk Factors, Clinical Features, Microbiological Profile, and Treatment Outcome.

PURPOSE: The purpose of this study was to evaluate the incidence, clinical features, microbiology, risk factors, and treatment outcomes in cases of ocular surface squamous neoplasia (OSSN) with coexisting microbial keratitis (MK). METHODS: This was a retrospective case-control study from a cohort of 939 cases with OSSN. RESULTS: Twenty eyes (2%) with OSSN and MK were included in the study group and 100 age-matched eyes with only OSSN as controls. Most common presentation was a combination of pain, redness, watering, and decreased vision (50%) over a median duration of 14 days. Mean corneal surface involvement by MK was 48% with corneal perforation in 6 cases (30%). Microbiology showed 10 culture positive cases for Gram-positive organisms (n = 5), fungus (n = 4), or mixed infection (n = 1). In the salvaged eyes, MK resolved in 9 eyes (90%) on medical treatment at a mean duration of 30 days and keratoplasty was performed in 1 eye. OSSN treatment included wide excisional biopsy (n = 9/18; 50%), extended enucleation (n = 7/18; 39%), and orbital exenteration in 1. Over a mean follow-up of 12 months, vision salvage was achieved in 7 of 18 (39%) and globe salvage in 10 of 18 (55%). Logistic regression analysis showed the following significant risk factors for MK in OSSN: male sex, human immunodeficiency virus seropositivity, increasing tumor diameter, limbal epicenter, temporal quadrant, noduloulcerative morphology, pigmentation, scleral invasion, keratin, and corneal component of the OSSN lesion. CONCLUSIONS: Rarely, MK can coexist with OSSN leading to a poor treatment outcome. Male sex, human immunodeficiency virus seropositivity, large limbal pigmented OSSN lesion with keratin and corneal component, noduloulcerative morphology, and scleral invasion were risk factors for this association.

Choroidal Thickness in Thyroid Eye Disease: Comparison With Controls and Application in Diagnosing Non-Inflammatory Active Disease.

Introduction Choroidal thickness is known to vary in various systemic diseases. In the current study, we aim to report the differences in choroidal thickness in thyroid eye disease (TED) and normals and its discriminatory value for differentiating various stages of TED. Methods Prospective, cross-sectional, non-interventional imaging study. In an institutional practice, 102 eyes of 51 patients were included and divided into five groups: normal controls (C), inactive TED (I), active TED (A), non-inflammatory active TED (NIA) and systemic thyroid disorder but no TED (SYS). Choroidal images were acquired using the swept-source optical coherence tomography (Topcon DRI OCT Triton) with automatic layer segmentation which provided an automatic measurement of the subfoveal choroidal thickness and the mean in nine subfields based on the Early Treatment Diabetic Retinopathy Study (ETDRS) grid. One-way analysis of variance (ANOVA), Youden index and area under the receiver operating characteristic curves (AUROC) were reported. Results Central choroidal thickness in the A group was 279±37.52 microns and in the NIA group was 302.5±59.22 microns. Both were comparable to each other and significantly higher than the C, I and SYS groups (p<0.001). All ETDRS sub-fields showed significant AUROC to distinguish NIA from I. Most significant Youden index was for the inner nasal and central ETDRS subfields (0.55 and 0.61 respectively). Inner nasal sub-field showed 100% specificity while the central sub-field, showed 86.5% for predicting NIA. At a choroidal thickness of >266 microns, the central sub-field had the strongest discriminatory potential to predict NIA.  Conclusion Choroidal thickness is greater in active and non-inflammatory active TED. The inner nasal and central ETDRS sub-fields have value in differentiating the non-inflammatory active TED eyes from the inactive eyes.

Comparative evaluation of clinical characteristics of biopsy-proven conjunctival intraepithelial neoplasia and invasive squamous cell carcinoma using image processing software programs.

PURPOSE: To identify morphological parameters aiding clinical differentiation of conjunctival intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (iSCC) and to demonstrate the utility of image processing software to objectively assess ocular surface squamous neoplasia (OSSN). METHODS: This retrospective case series included all biopsy-proven cases of OSSN presenting as an ocular surface nodule. Based on histopathology, lesions were classified as CIN and iSCC. Clinical image analysis utilized 'Contour' and 'ImageJ' software. The effect of predictors demography, seropositivity, lesion dimensions, keratin, pigmentation, corneal involvement, vascularity and feeder vessels on the final histopathologic grade were assessed. RESULTS: A total of 108 OSSN lesions (74 CIN and 33 iSCC) were included. Mean age was 46.1 ± 17.2 years in CIN and 47.2 ± 13.9 years in iSCC. By univariate logistic regression analysis, significant predictors of iSCC were HIV seropositivity (p < 0.0001), maximum diameter (p = 0.003), perpendicular to maximum diameter (p = 0.003), height (p = 0.003), nodular morphology (p = 0.006) and feeder vessels (p = 0.03), whereas gelatinous morphology (p = 0.02) was predictor of CIN. By multiple logistic regression, seropositivity was the predictor of iSCC (p < 0.0001, OR 13.33 ± 8.35, 95% CI 3.90-45.53). CONCLUSION: HIV seropositivity is an important predictor of iSCC. Large, thick, nodular lesions with feeder vessels may favor the diagnosis of iSCC, whereas gelatinous, small, flatter lesions without feeder vessels may favor CIN. In a first of its kind study, simple and objective analysis of OSSN with image processing software was demonstrated.

Intra-orbital fat necrosis following transcaruncular orbitotomy mimicking a surgical site infection: A case report.

Fat necrosis is a benign non-suppurative inflammation of adipose tissue most commonly occurring in breast, subcutaneous tissue or intraabdominal fat post trauma, surgery, radiation. Transcaruncularorbitotomy provides a safe, rapid, and cosmetically pleasing approach to the medial wall and orbital apex. Intraorbital fat necrosis as its complication has not been documented in literature. The authors report the case of an elderly lady who presented with localized pain, swelling following a transcaruncular orbitotomy for excision biopsy of an orbital vascular mass. The etiology, clinical presentation, intraoperative finding, imaging, and possible mechanisms contributing to the pathogenesis of postsurgical orbital fat necrosis has been suggested.

Preoperative embolisation of orbital solitary fibrous tumour.

Solitary fibrous tumours (SFT) is an encompassing terminology comprising of tumours with proliferating CD34 positive specialised fibroblasts. Orbital SFTs are rare slowly progressive highly vascular neoplasms. Complete surgical excision is considered the mainstay treatment. Incomplete resection is a known risk factor for recurrence and malignant transformation. Recently preoperative embolisation of SFT has shown promising results in reducing the vascularity of these tumours rendering them amenable to complete surgical excision. Less than 10 cases of embolisation of orbital solitary fibrous tumours have been described in literature. Our patient underwent an attempted surgical excision elsewhere with significant intraoperative haemorrhage which precluded its complete excision. Herein, we report successful outcome in a case of hypervascular orbital SFT managed with preoperative embolisation, surgical resection and adjuvant radiotherapy along with a review of relevant literature.

Posterior uveal melanoma in 321 Asian Indian patients: analysis based on the 8th edition of American Joint Committee Cancer classification.

PURPOSE: To evaluate the presenting features, treatment, and outcomes of posterior uveal melanoma (PUM) in Asian Indians based on the 8th edition of American Joint Committee on Cancer (AJCC) classification. METHODS: Retrospective interventional case series of 321 Asian Indian patients with PUM. RESULTS: Based on AJCC, PUM was classified into categories T1 (n = 36; 11%), T2 (n = 74; 23%), T3 (n = 126; 39%), and T4 (n = 85; 27%). Regarding tumor features, T4 was more likely to have pre-equatorial epicenter (vs T1 and T2; p ≤ 0.011), iris abnormalities (vs T2 and T3; p ≤ 0.002), and extraocular tumor extension (vs T3; p = 0.001), whereas T1 was more likely to have macular epicenter (vs T2, T3, T4; p ≤ 0.013), lipofuscin deposits (vs T3 and T4; p ≤ 0.008), and amelanotic tumors (vs. T4; p = 0.003). On multivariate analysis, factors predictive of systemic metastasis were increasing tumor thickness (p = 0.002) and extraocular tumor extension (p = 0.009). The 5-, 10-, and 15-year melanoma-related metastases rates were 0%, 0%, and 0% in T1, 0%, 60%, and 60% in T2, 7%, 40%, and 70% in T3 and 13%, 36%, and 76% in T4, respectively. Risk for metastasis was 1.23 times more for every 1-mm increase in tumor thickness and 9 times more with extraocular tumor extension. CONCLUSION: The AJCC 8th edition provides prognostic classification for PUM in Asian Indian patients. The significant risk factors for metastasis were increasing tumor thickness and extraocular tumor extension.

Retained intraorbital wooden foreign body presenting with combined anterior and posterior scleritis.

Penetrating injury of the orbit with a wooden stick is not an uncommon finding in ocular emergencies. A 36-year-old man presented with redness, pain in the left eye following fall from a motorcycle 3 days ago. Ocular examination showed features of combined anterior and posterior scleritis in the form of an anterior scleral nodule, retinal folds and T sign on ultrasonography. There was worsening of symptoms along with new onset diplopia following scleral deroofing which led to the suspicion of an intraorbital wooden foreign body (IOWFB). CT scan of orbit showed a well-defined hypodensity between the medial rectus and optic nerve resembling a pocket of air surrounded by a rim of hyperdensity. IOWFB was removed under direct visualisation via transconjunctival orbitotomy. This is the case of a missed retained IOWFB presenting with features of combined anterior and posterior scleritis.

Management of Intra-orbital Wooden Foreign Bodies at a Resource-limited Setting in Sub-Saharan Africa.

Introduction: Wooden intra-orbital foreign bodies (IOrbFBs) have a high risk of microbial contamination needing timely diagnosis and treatment. We describe management of three cases of wooden IOrbFB at a resource-limited setting in Liberia. Materials and Methods: This is a retrospective case series of three patients with IOrbFB managed at the Liberia Eye Center, Monrovia, Liberia. Demographic details, mode of injury, ocular examination findings, neuroimaging, surgical treatment, and clinical findings on post-operative follow-up visits were noted for each patient. Results: All the three patients were young, male, and were involved in traumatic incidents (fall in two cases and road traffic accident in one case). Two patients with visible wooden FB presented within 48 h of injury and one patient with occult FB presented after 2 weeks. All patients underwent orbital imaging followed by surgical exploration for the removal of FB. One patient also had coexisting orbital cellulitis, which was successfully treated medically. One of these patients had best corrected visual acuity of 20/20, and the other two had no perception of light in the affected eyes. Conclusion: History of injury with a wooden material should raise a high index of suspicion for an occult IOrbFB. Timely diagnosis and treatment of wooden IOrbFB can be challenging in a resource-limited setting, but with a systematic approach they can be treated satisfactorily.

Introduction: Les corps étrangers intra-orbitaires en bois présentent un risque élevé de contamination microbienne nécessitant un diagnostic et un traitement rapides. Nous décrivons la prise en charge de 3 cas de corps étrangers intra-orbitaires en bois dans un pays aux ressources limitées tel quel le Libéria. Matériel et méthodes: Cest une étude rétrospective sur 3 cas de Corps étrangers intra orbitaire en bois prise en charge dans le centre oculaire du Libéria situé à Monrovia. Les détails démographiques, le mode de blessure, les résultats de l'examen oculaire, la neuro-imagerie, le traitement chirurgical et les résultats cliniques lors des visites de suivi post-opératoires ont été notés pour chaque patient. Résultats: Les 3 patients étaient jeunes, de sexe masculin et ont été impliqués dans des incidents traumatiques (chute dans 2 cas, et accident de la voie publique dans un cas). Deux patients avec un corps étranger en bois visible se sont présentés dans les 48 heures suivant la blessure et un patient avec un corps étranger occulte s'est présenté après 2 semaines. Tous les patients ont été soumis à une imagerie orbitaire suivie d'une exploration chirurgicale pour l'élimination du corps étranger. L'un de ces patients avait une acuité visuelle corrigée de 20/20 et les deux autres n'avaient aucune perception de la lumière dans les yeux affectés. Conclusion: La notion de traumatisme par un matériau en bois devrait faire craindre un Corps étranger intra orbitaire occulte. Le diagnostic et le traitement rapides des corps étrangers intra-orbitaire en bois peuvent être difficiles dans un contexte de ressources limitées, mais avec une approche systématique, ils peuvent être traités de manière satisfaisante.