Quality and applicability of cadaveric donor eyes for molecular biology research: An Indian experience.

PURPOSE: Human ocular tissue banking plays an important part in the advancement of translational research for identifying the molecular processes involved in disease etiology and pathogenesis. Timely obtaining a good-quality ocular tissue from a cadaveric donor is exceedingly difficult, especially in remote areas, with a variable transportation time (within 12-24 h), raising concerns about RNA quality and its subsequent applications. Therefore, we assessed the utility of retinal tissues from cadaver donor and enucleated eyes based on the RNA quality and gene expression by real-time polymerase chain reaction (PCR). SETTINGS AND DESIGN: Prospective study. METHODS: Retina tissues were separated from the donor/enucleated eyes received in the eye bank within 24 h of death (n = 15) and within an hour from OR (n = 3), respectively, and stored immediately at -80 degree. RNA was isolated using trizol, and the quantity and quality were assessed using Qubit and agarose gel electrophoresis, respectively. QPCR was performed for measuring the expression of different retinal-specific genes. The cellular viability of the retina was assessed by establishing explant primary cell cultures. STATISTICAL ANALYSIS: The data were calculated as an average of normalised Ct values ± standard error of the mean. RESULTS: RNA obtained from cadaveric tissues despite being partially degraded showed a uniform strong gene expression of several retinal-specific genes such as PAX6, RHO, TUBB3, CRX , and ALDH1L1 . The primary cultures established from cadaveric tissues showed viable cells. CONCLUSION: The cadaver donor tissues collected within 24 hours of death can be effectively utilized for gene expression profiling.

Open Globe Injuries with Concurrent Orbital Fractures - Clinical Settings and Factors Predicting Outcomes.

AIM: We describe the clinical settings and the factors predicting outcomes in open globe injuries with concurrent orbital fractures. METHODS: Retrospective, consecutive, non-comparative study. All eyes from January 2014 to January 2021 with concurrent open globe injuries with orbital fractures that underwent management were included. The clinical data of each patient who underwent a comprehensive ophthalmic examination was entered into a browser-based electronic medical records system (eyeSmart EMR) by uniformly trained ophthalmic personnel and supervised by an ophthalmologist using a standardized template. Favorable functional outcome was defined as the final best corrected visual acuity of >20/200 as per the World Health Organization (WHO) definitions of severe visual impairment and blindness. A favorable anatomic outcome was defined as preservation of the globe, absence of hypotony, attached retina, and absence of active inflammation at the last visit. Multivariate logistic regression analysis was done to assess the effect of various demographic and clinical factors and the type of orbital fracture on the final anatomic and functional outcome. RESULTS: Ninety-one eyes of 91 patients were included in the study. Females accounted for 74/91 (81.3%) of the eyes. Modes of trauma was rupture in 67%, perforating in 5.5% and penetrating in 27.5% of the cases. Orbital rim involvement was seen in 79.1%. The most common isolated fracture seen was a medial wall (19.78%), which was followed by the orbital floor (15.38%). Favorable functional outcome was seen in 10 eyes (11%), while a favorable anatomic outcome was achieved in 45 (49.5%). Odds of a favorable functional outcome were 6.12 (95% CI 1.22 to 30.71), p = .02 for an open globe injury with orbital fracture in the absence of a concurrent retinal detachment. Odds of a favorable anatomic outcome were 55.55 (95% CI 2.43 to 1250), p = .01 when the injury did not involve zone 3, 9.94 (95% CI 2.05 to 48), p = .004 when concurrent retinal detachment was absent, 16.3 (95% CI 1.42 to 187.19), p = .02 when the orbital rim was intact and 7.83 (95% CI 1.09 to 56.19), p = .04 when only one orbital wall was involved. CONCLUSIONS: Open globe injuries with concurrent orbital fractures result in a very poor functional outcome. Concurrent retinal detachment is a negative predictive factor. Associated fractures involving the orbital rim increase the risk of eyeball loss.

Orbito-cranial schwannoma-a multicentre experience.

OBJECTIVES: To describe the features, management approaches, and outcomes of orbito-cranial schwannomas. METHODS: Retrospective review of ten patients with orbito-cranial schwannomas managed in six orbital services over 22 years. Data collected included demographics, presenting features, neuroimaging characteristics, histology, management approach, complications, and outcomes. RESULTS: Mean age of the patients was 41.4 ± 19.9 years, and 6 (60%) were females. The majority presented with proptosis (90%), limited extraocular motility (80%), eyelid swelling (60%), and optic neuropathy (60%). Most lesions (80%) involved the entire anterior-posterior span of the orbit, with both intra- and extraconal involvement. All tumours involved the orbital apex, the superior orbital fissure, and extended at least to the cavernous sinus. Surgical resection was performed for all. Seven (70%) of the tumours were completely or subtotally resected combining an intracapsular approach by an orbital-neurosurgical collaboration, with no recurrence on postoperative follow-up (6-186 months). Three underwent tumour debulking. Of these, two remained stable on follow-up (6-34 months) and one showed progression of the residual tumour over 9 years (cellular schwannoma on histology) necessitating stereotactic radiotherapy (SRT) for local control. Adjuncts to the orbito-cranial resection included perioperative frozen section (n = 5), endoscopic transorbital approach (n = 2), and image-guided navigation (n = 1). Post-surgical adjuvant SRT was used in three subjects. CONCLUSIONS: These results highlight the possibility of successful surgical control in complex orbito-cranial schwannomas. A combined neurosurgical/orbital approach with consideration of an intracapsular resection is recommended. Recurrence may not occur with subtotal excision and observation may be reasonable. Adjunctive SRT for progression or residual tumour can be considered.

Two-Year Outcomes of Transcutaneous Non-Image Guided Bleomycin Sclerotherapy in Conjunctival Lymphatic Malformations: A Protocol-Based Management in 16 Eyes.

OBJECTIVES: To study the efficacy and the 2-year outcomes of treating conjunctival lymphatic malformations (LM) with protocol-based bleomycin sclerotherapy. METHODS: A retrospective interventional study of 16 eyes with conjunctival LM treated with bleomycin sclerotherapy between December 2016 and 2019. A clinical resolution was assessed as poor (less than 25% decrease in size), fair (25%-50% decrease in size), good (50%-75% decrease in size), excellent (more than 75% decrease in size), and complete resolution. RESULTS: Mean age at presentation was 18 ± 13.09 (15 years, 3 to 59 years) years. The conjunctival component was classified based on clinical appearance as conjunctival mass (12) and microcystic LM (4). Mean clock hours of involvement were 3.32 ± 5.29 clock hours (4, 2-9 clock hours). An average per session dose of 1.8 ± 0.3 IU (median 2 IU, range 1-2 IU) and a cumulative dose of 3 ± 1.5 IU (3, 1-6 IU) of bleomycin were injected over an average of 1.6 ± 0.7 (median 2, range 1-3) treatment sessions per patient. Excellent response was observed in 11 (69%) cases. A residual lesion requiring surgical debulking was noted in 1 case. Recurrence was noted in 2 (13%) cases one of which was treated with repeat sclerotherapy resulting in complete resolution. Adverse reactions included restricted extraocular motility in extreme gaze in 2 eyes (13%). Sustained tumor resolution was observed over a mean follow-up of 29.24 + 9.45 months (24, 24-38 months). CONCLUSIONS: Bleomycin sclerotherapy gives excellent response in conjunctival LMs and is an effective first-line therapy in these cases.

Demography, Clinical Settings and Outcomes in Evisceration with Implant: An Electronic Medical Records Driven Analytics of 2071 Cases.

PURPOSE: To describe the demography, clinical settings and outcomes in 2071 patients undergoing evisceration across a multi-tier ophthalmology hospital network and comparison of results with the global scenario of clinical settings for evisceration. METHODS: An analysis of 2071 patients undergoing evisceration and implant between 2013 and 2019. RESULTS: The mean age at surgery was 39 ± 22 years. Children constituted 303(15%) of the cases. The four leading indications for surgery included painful blind eye in 760(37%), phthisis bulbi in 552(27%), staphyloma in 215(10%) and open globe injury in 195(9%) patients. The clinical settings encountered were trauma in 852(41%), ocular infection in 714(34%), glaucoma in 198(10%), post ocular surgery in 146(7%), congenital in 95(5%) and uveitis in 21(1%). Trauma and infection remained the commonest clinical settings in the urban (843,75%), rural (622,77%) and metropolitan (101,71%) areas. Decade wise distribution suggested trauma to be the commonest clinical setting in the first 4 decades and infection in the next 6 decades. The mean follow-up period was 351 ± 386 days (median 194). While trauma remained one of the commonest clinical setting in both the developed and the developing economies, painful blind eye and intractable glaucoma were other common clinical settings in the developed economies and infection was one of the leading clinical setting in the developing economies. CONCLUSION: Most patients undergoing evisceration are young. The commonest indications for surgery include painful blind eye and phthisis bulbi. Trauma and infection remain the commonest clinical settings for evisceration in developed and developing economies.

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.

Immunopathology of COVID-19 and its implications in the development of rhino-orbital-cerebral mucormycosis: a major review.

PURPOSE: To present a literature review on various immunopathologic dysfunctions following COVID-19 infection and their potential implications in development of rhino-orbital-cerebral mucormycosis (ROCM). METHODS: A literature search was performed via Google Scholar and PubMed with subsequent review of the accompanying references. Analogies were drawn between the immune and physiologic deviations caused by COVID-19 and the tendency of the same to predispose to ROCM. RESULTS: Sixty-two articles were reviewed. SARS-CoV-2 virus infection leads to disruption of epithelial integrity in the respiratory passages, which may be a potential entry point for the ubiquitous Mucorales to become invasive. COVID-19 related GRP78 protein upregulation may aid in spore germination and hyphal invasion by Mucorales. COVID-19 causes interference in macrophage functioning by direct infection, a tendency for hyperglycemia, and creation of neutrophil extracellular traps. This affects innate immunity against Mucorales. Thrombocytopenia and reduction in the number of natural killer (NK) cells and infected dendritic cells is seen in COVID-19. This reduces the host immune response to pathogenic invasion by Mucorales. Cytokines released in COVID-19 cause mitochondrial dysfunction and accumulation of reactive oxygen species, which cause oxidative damage to the leucocytes. Hyperferritinemia also occurs in COVID-19 resulting in suppression of the hematopoietic proliferation of B- and T-lymphocytes. CONCLUSIONS: COVID-19 has a role in the occurrence of ROCM due to its effects at the entry point of the fungus in the respiratory mucosa, effects of the innate immune system, creation of an environment of iron overload, propagation of hyperglycemia, and effects on the adaptive immune system.

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.

Local Infiltration Anesthesia for Orbital Exenteration in Patients With Rhino-Orbital Cerebral Mucormycosis: A Case Series.

Orbital exenteration is occasionally required for rhino-orbital cerebral mucormycosis. Multiple associated comorbidities can pose a risk for general anesthesia. There is only 1 report of exenteration being performed under trigeminal nerve block. We describe 5 patients who underwent orbital exenteration under local infiltration anesthesia with sedation. Patients and surgeons reported satisfactory conditions, with stable hemodynamics and successful day care management. Orbital exenteration under local infiltration anesthesia can be a safe and effective alternative for patients with rhino-orbital mucormycosis who are at risk with use of general anesthesia.

Evidence of dengue virus in eviscerated specimens of panophthalmitis secondary to dengue fever: A possible cause-effect phenomenon.

PURPOSE: To report a retrospective series of three cases of infectious panophthalmitis post-dengue fever with ex vivo confirmation of dengue virusribonucleic acid (RNA) in the tissues of the eye. METHODS: Four eyes of three patients, who were diagnosed with panophthalmitis following dengue fever and who underwent evisceration, were included. All demographic and clinical data were recorded. The eviscerated samples were subjected to direct microscopy, culture for bacteria, fungi, and parasites, and molecular virology (dengue virus [DENV] NS1-specific reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay). RESULTS: The time from the development of dengue fever to the occurrence of ocular symptoms was 4.33 ± 1.15 (median 5) days. DENV NS1 RNA, suggestive of the presence of the dengue virus, was confirmed in all evisceration specimens (uveal tissue, cornea). All the patients recovered completely from dengue fever and on follow-up had healthy eviscerated sockets. CONCLUSION: Demonstration of the DENV RNA in the eviscerated specimens of panophthalmitis following dengue fever implicates the DENV in the pathophysiology of the ocular infection.

Choroidal vascularity index in thyroid eye disease: comparison with controls and application in diagnosing non-inflammatory active disease.

PURPOSE: To report the differences in choroidal vascularity index (CVI) 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. Ninety-four eyes of 54 patients were included and divided into 5 groups - normal controls (C), inactive TED (I), active TED (A), non-inflammatory active TED (NIA) and systemic hyperthyroid disorder but no TED (SYS). Choroidal images were acquired using the swept-source optical coherence tomography and the choroid was binarized to calculate the CVI. RESULTS: Ninety-four eyes were included. Mean age was 44.52 ± 10.02 years (median 46 years, range 19-65 years). Mean IOP was 16.1 ± 3.37 mm Hg (median 16 mm Hg, range 16-24 mm Hg). Mean Spherical equivalent (SE) was -0.08 ± 1.86 diopters (median 0, range -2.5 to +2.25). Intra-rater agreement was 0.84 (p < 0.001). Inter-rater agreement was noted to be 0.85 (p < 0.001) for consistency and 0.77 (p < 0.001) for absolute agreement. CVI in the A group was 70.11 ± 3.38% and in the NIA group was 69.32 ± 3.5%. Both were comparable to each other and significantly higher than the C, I and SYS groups (p < 0.001). Multiple regression showed that the Clinical Activity Score (CAS) had a positive effect and spheroequivalent had a negative effect on the CVI. At CVI of 66.83%, active TED can be diagnosed with sensitivity of 91.67% and specificity of 82.14%                 . CONCLUSIONS: CVI is significantly higher in active TED and NIA TED compared to other groups. It has a good value in differentiating the non-inflammatory active TED eyes from the inactive eyes.

Retinal vascularity, nerve fiber, and ganglion cell layer thickness in thyroid eye disease on optical coherence tomography angiography.

PURPOSE: To compare the retinal vascularity, peripapillary vascularity, nerve fiber layer thickness and ganglion cell layer thickness between active, inactive thyroid eye disease (TED) and healthy eyes. METHODS: Retrospective comparative cross-sectional cohort study. Patients with TED, active and inactive on the VISA score, and healthy eyes were included. All patients underwent optical coherence tomography angiography with detailed demographic and clinical data capture. Using automated software, retinal and peripapillary vascularity index, nerve fiber layer thickness, and ganglion cell layer thickness were calculated and were compared between the groups. RESULTS: Twenty-four eyes with active TED, 102 eyes with inactive TED and 52 healthy eyes were included. Independent sample t test was used to compare parametric data and Mann-Whitney test to compare non-parametric data. The age and gender were comparable across groups. The peripapillary vascularity index (26.82 ± 4.13 versus 34.92 ± 5.08, p = .002) and the macular vascularity index (20.32 ± 2.5 versus 31.21 ± 3.89, p < .0001) were reduced in active TED eyes versus inactive eyes. Macular vascularity index was comparable in the inactive versus the healthy eyes. The RNFL thickness was increased in the active TED eyes versus the inactive eyes (45.11 ± 18.3 versus 35.55 ± 7, p = .03) and active versus healthy eyes (45.11 ± 18.3 versus 36.28 ± 7.89, p = .03). Ganglion cell layer thickness between all three groups was comparable. CONCLUSION: Decrease in peripapillary and macular vascular density and increase in RNFL thickness are seen in active TED compared to inactive TED and healthy eyes. In disease inactivity, these parameters are comparable to healthy eyes.

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.

Transcutaneous retrobulbar injection of amphotericin B in rhino-orbital-cerebral mucormycosis: a review.

Mucormycosis is an aggressive and potentially fatal invasive fungal infection. The most common form of mucormycosis is rhino-orbital-cerebral mucormycosis (ROCM). While it is commonly seen in immunocompromised patients, it is also known to affect healthy individuals. The global disease burden of ROCM has increased significantly following the surge in cases during the COVID-19 pandemic. Endoscopic sinus debridement, systemic antifungal therapy, and control of the underlying immunosuppressive condition are essential for the management of ROCM. Orbital involvement, however, presents a challenge to clinicians. Intervention strategies that have been described to treat orbital disease include orbital exenteration, conservative orbital debridement with or without irrigation with amphotericin B and transcutaneous retrobulbar injection of amphotericin B (TRAMB). Currently, there is a lack of clarity regarding the indications and outcomes of TRAMB as a treatment modality. In this review, the drug formulations used, the complications, and outcomes of previously described cases that have used TRAMB in cases of ROCM are discussed. Favorable outcomes following TRAMB depend on appropriate patient selection and radiological evidence of the orbital burden of the disease. This review aims to familiarize clinicians with objective parameters for patient selection for TRAMB, namely the extent of the disease, the clinical features, and radiological findings; viz. the clinical interpretation of areas of contrast uptake and those of necrosis. TRAMB can be considered as a viable option in select cases of orbital mucormycosis where exenteration or debridement are not indicated, or when there is limited orbital disease.

Outcomes and complications of evisceration with primary implant: an electronic medical record driven analytics of 1800 cases.

PURPOSE: To describe the surgical outcomes and implant complications in 1,800 patients undergoing evisceration with primary implant. METHODS: An Electronic Medical Record-driven analysis of 1,800 patients undergoing evisceration with primary implant between 2013 and 2019. Implant sizing was performed intra-operatively to place the largest implant without tension on the wound closure. Outcome measures included implant complications, prosthesis measurements, and incidence of a good aesthetic outcome. Good outcome was defined as <2 mm enophthalmos and grade 1 or less superior sulcus deformity with a custom ocular prosthesis. RESULTS: Eighteen hundred eyes of 1800 patients were included. The mean age at surgery was 36 ± 21 years (median 32 years). Implants used were poly(methyl methacrylate) (PMMA) in 1737 (97%) and porous polyethylene in 63 (3%) patients. Two-petal sclerotomy was performed in 1512 (88%) and four-petal sclerotomy in 165 (10%) patients. The mean diameter of the implant used was 19.35 ± 1.18 mm (median 20, range 10-22 mm). The implant extrusion rate was 3% (56) and implant displacement was seen in none. The mean prosthesis volume and thickness were 2.22 ± 0.67 ml (median 2, range 1-6.5 ml) and 6 ± 1 mm (median 6, range 2-9 mm). The mean difference in prosthesis projection on Hertel's exophthalmometer was 0.28 ± 1 mm (median 0, range 0-1 mm). Good outcome was observed in 93%. The mean follow-up period was 351 ± 386 days (median 194). CONCLUSION: Evisceration with empirically selected primary orbital implant placement is associated with minimal implant complications and gives a good aesthetic outcome in 93% of the patients.

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.

Rhino-orbital mucormycosis following COVID-19 in previously non-diabetic, immunocompetent patients.

PURPOSE: To report a series of 13 immunocompetent patients who developed new-onset uncontrolled diabetes mellitus (DM) following COVID-19 infection and presented as rhino-orbital mucormycosis (ROM). METHOD: Retrospective study. RESULTS: A total of 127 patients of COVID-19 Associated Mucormycosis (CAM) were evaluated at four centres in India. All patients underwent endoscopic sinus debridement surgery and received systemic amphotericin-B therapy. Five patients (5/13; 38.4%) received retrobulbar amphotericin-B injections. Orbital exenteration was performed in advanced orbital involvement or progression of orbital disease in spite of maximal medical therapy. In his cohort, 13/127 (10.2%) patients presented with new onset DM, where one patient had bilateral disease. The mean age was 35.9 years (range: 20-51 years) and the mean duration from diagnosis of COVID-19 to the diagnosis of mucormycosis was 14.2 days. While 7/13 (53.8%) of the patients received systemic corticosteroids during the course of their treatment for COVID-19, six patients received no steroids or immunomodulators. The mean follow-up period was 9.2 weeks (range: 3-18 weeks) following discharge. Life salvage was possible in 100% of the cases. While overall globe salvage was possible in 42.8% (6/14 eyes), the globe could be preserved in 4/5 patients who received retrobulbar amphotericin-B injections. CONCLUSIONS: Those involved in the care of COVID-19 patients should be aware about the possibility of recent-onset DM, even in patients without a history of corticosteroid therapy. Rarely, recent-onset DM following COVID-19 may present as rhino-orbital mucormycosis, which requires aggressive surgical and medical intervention.

Clinical Presentations, Management and Outcomes of Rhino-Orbital-Cerebral Mucormycosis (ROCM) Following COVID-19: A Multi-Centric Study.

PURPOSE: To report clinical presentations and factors affecting outcomes in rhino-orbital-cerebral mucormycosis following COVID-19. METHODS: Retrospective multi-centric interventional case series of 58 eyes with rhino-orbital-cerebral mucormycosis. Demography, clinical parameters and management outcomes were noted. Factors affecting outcome and mortality were analyzed. Outcome was defined as favorable when complete resolution or stabilization without further progression of the infection was noted at last visit. RESULTS: Mean age was 55 ± 11 years (median 56). The mean HbA1c value was 10.44 ± 2.84 mg% (median 10.5). The duration between the diagnosis of COVID-19 and rhino-orbital-cerebral mucormycosis was 16 ± 21 days (median: 8 days). Thirty-six eyes (62%) had no vision at presentation. Imaging revealed paranasal sinus involvement (100%), orbital apex involvement (41%), cavernous sinus involvement (30%), and central nervous system (CNS) involvement (33%). All the patients were treated with systemic Liposomal amphotericin-B and sinus debridement. Twenty-two eyes (38%) underwent exenteration. One eye underwent transcutaneous retrobulbar amphotericin-B. The mean follow-up duration was 5.62 ± 0.78 months (median 6). Favorable outcome was seen in 35 (60%) cases. Presence of uncontrolled diabetes (p = 0.001), orbital apex involvement (p = 0.04), CNS involvement (p = 0.04), and history of steroid use (p < 0.0001) resulted in unfavorable outcome. CNS involvement was the only factor predicting mortality (p = 0.03). Mortality was seen in 20 (34%) patients. CONCLUSION: Over a third of patients with rhino-orbital-cerebral mucormycosis following COVID-19 have an unfavorable clinical outcome. Uncontrolled diabetes mellitus at presentation, involvement of the orbital apex, CNS, and the usage of steroids were associated with poorer outcomes. CNS involvement was a factor determining mortality.