Late postoperative vitreous cavity hemorrhage after vitrectomy for proliferative diabetic retinopathy-observation versus intervention.

PURPOSE: To analyze the outcome of intervention versus observation for vitreous cavity hemorrhage occurring after a 2-month period of blood-free cavity (late postoperative vitreous cavity hemorrhage-POVCH) in eyes operated by vitrectomy for complications of proliferative diabetic retinopathy (PDR). METHODS: This study was a 10-year retrospective, observational, multi-center study involving eight major vitreoretinal surgical centers across India from January 2010 to December 2019. The primary objective of the study was to assess the visual and clinical outcomes of various management approaches for late POVCH. The key secondary objective was to determine the best management option that prevented recurrence. Patients with follow-up of less than 6 months of POVCH management were excluded. RESULTS: The occurrence of late POVCH was studied in 261 eyes. The median time to occurrence was 7 months (range: 2-87) postvitrectomy/silicone oil removal. The majority (58%) experienced a single, nonrecurring POVCH event. Visual acuity outcome was independent of all management approaches (P = 0.179; mean follow-up 20.7 ± 14.1 months). With watchful observation, spontaneous resolution was noted in 83% (60/72 eyes) of eyes in 81.5 days (interquartile range, 169.75). Silicone oil injection was most effective in preventing recurrence (P < 0.001). CONCLUSION: The current treatment practice of late POVCH management in PDR suggests that watchful observation for at least 3 months could be as efficacious as any surgical intervention.

Relevance of multicolor imaging, its component channels, and fundus autofluorescence in describing macular telangiectasia type-2 (MacTel) lesion characteristics.

PURPOSE: The aim of the study was to describe imaging characteristics and detection rates of phenotypic features in macular telangiectasia type-2 (MacTel) on multicolor (MC), blue reflectance (BR), green reflectance (GR), infrared reflectance (IR), and fundus autofluorescence (FAF) and to evaluate sensitivity, specificity, and predictive values across modalities. METHODS: In this monocentric observational study, 282 eyes of 148 patients with MacTel underwent color fundus photograph, MC, BR, GR, IR, FAF, spectral-domain optical coherence tomography (SD-OCT), OCT-angiography (OCT-A), and fundus fluorescein angiography (FFA). Grading was done by two graders qualitatively and quantitatively for the presence of the following prespecified MacTel findings [crystals, right-angle vessels (RAVs), plaques, subretinal neovascularization (SRNV), and MacTel area]. Across each imaging modality, the detection rate of RAVs and SRNV was compared with reference standard OCT-A (RAVs and SRNV) and FFA (SRNV), whereas that of plaques was compared with reference standard SD-OCT. RESULTS: MC identified overall MacTel characteristics in 92.7% of eyes. Regarding the presence, number, and quadrants of RAVs and the presence and number of crystals, MC and GR had superior detection rates as well as the highest sensitivity and negative predictive value. Retinal plaques were better detected using FAF (97%), followed by MC (88%). In proliferative MacTel, SRNV was identified in 86% and 79% of eyes on MC and IR, respectively. While BR clearly delineated MacTel area in 100% eyes, FAF was able to ascertain a larger area of involvement in proliferative MacTel. CONCLUSION: The findings demonstrate the ability of MC, its component channels, and FAF to describe MacTel characteristics qualitatively and quantitatively.

Type-3 macular neovascularization in a case of long-standing macular telangiectasia type-2.

We report a rare case of type-3 macular neovascularization (MNV) in an established case of macular telangiectasia type-2 (MacTel). A 49-year-old healthy Indian woman was diagnosed with MacTel (Gass and Blodi stage 3 in the right eye [OD] and stage 2 in the left eye [OS]) in our retina clinic in January 2004. She was subsequently seen 10 years later with MacTel progression in OD (stage 4) and drusenoid changes in both eyes. She recently complained of sudden onset diminution of vision in OS of 1 week duration. The best-corrected visual acuity, when she attended this day, was 20/500 (OD) and 20/60 (OS). Fundus revealed pigment deposition in the macula in OD and a large pigment epithelial detachment (PED) in OS with drusen in both eyes, suggesting coexisting age macular degeneration (AMD) and MacTel (stage 4 OD; stage 2 OS) bilaterally. Multimodal imaging with spectral-domain optical coherence tomography showed drusen, a large trapezoid PED with central apical disruption, outer retinal hyperreflective material, intraretinal fluid, and inner retinal cavitation. Indocyanine green angiography revealed "hotspot" at center of the PED with hairpin-loop vessels. Optical coherence tomography angiography demonstrated network at apex of the PED. These features confirmed a diagnosis of type-3 MNV (classical retinal angiomatous proliferation [RAP] lesion) in OS along with features of AMD and MacTel. There was resolution of intraretinal fluid and reduction in height of PED following three loading doses of intravitreal ranibizumab in OS. Although type-3 neovascularization has been described in MacTel, to the best of our knowledge, this is the first documentation of classical RAP features of MNV with all described multimodal imaging features. The type-3 neovascularization typically described in association with MacTel is retinal-retinal, retinal-subretinal, and retinochoroidal anastomosis (RCA). Although RAP is also associated with RCA, the features seen in our case, i.e., triad of erosion at the roof of PED, inverted flap in the PED, and hotspot in the center of PED, have not been documented in association with MacTel.

Role of cystatin C in the detection of sight-threatening diabetic retinopathy in Asian Indians with type 2 diabetes.

AIM: To study the association between cystatin C and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2DM). METHODS: In a cross-sectional study carried out at two tertiary centres in India in 2022, individuals with T2DM underwent clinical and ophthalmic assessments and estimation of serum cystatin C. Grading of DR was done by retina specialists. STDR was defined by the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) and/or diabetic macular edema. Receiver operating characteristic (ROC) curves were used to identify cystatin C cut-off value for detecting STDR. RESULTS: Among 420 individuals with T2DM (mean age 56 ± 9 years; mean duration of diabetes 14.5 ± 7.9 years), 121 (24.1 %) had No-DR, 119 (28.3 %) had No-STDR and 200 (49.6 %) had STDR. Mean cystatin C level was significantly higher in individuals with STDR compared to those with no-STDR and No-DR (1.34 vs 1.06 vs 0.93 mg/L, p < 0.001). Cystatin C cut-off value ≥1.11 mg/L had a C statistic of 0.944 (95 % CI: 0.909-0.968, p < 0.001), 96.8 % sensitivity and 78.2 % specificity for detection of STDR. CONCLUSION: Elevated serum cystatin C was strongly associated with STDR and could possibly be used as a biomarker for screening for sight-threatening diabetic retinopathy.

Relation of interdigitation zone changes and right-angle vessels in Macular Telangiectasia Type-2 (MacTel).

BACKGROUND: To study the relation between interdigitation zone (IDZ) and right-angle vessel (RAV) in Macular Telangiectasia Type-2 (MacTel). METHODS: A total of 43 eyes of 38 patients with presence of definite RAV on colour fundus photograph (Gass and Blodi-only stage-3) were confirmed on multimodal imaging. The relation of IDZ changes and associated ellipsoid zone (EZ) alterations on spectral-domain optical coherence tomography (OCT) with RAV were studied at baseline and these OCT changes were followed up in 15 eyes over a mean of 3.86 years. RESULTS: A total of 58 RAVs were found in the 43 eyes and 53/58 (91.3%) RAVs were associated with IDZ alterations in 39 eyes. On follow-up, IDZ attenuation progressed to IDZ loss and subsequent EZ attenuation and loss. A pre-existing IDZ loss was associated with subsequent EZ defect (P = 0.002). In 36 eyes that had OCT angiography, eyes with RAV showed deep capillary plexus telangiectasia in all 36 (100%) eyes and 32/36 (89%) eyes showed IDZ changes with or without EZ loss. CONCLUSIONS: IDZ attenuation and/or loss are associated with RAV and may serve as predictor of EZ loss in MacTel.

OUTER FOVEAL DEFECTS IN TYPE-2 MACULAR TELANGIECTASIA.

PURPOSE: To report characteristics of outer foveal defects (OFDs) in type-2 macular telangiectasia (MacTel) on spectral domain optical coherence tomography. METHODS: This was a single-center observational study. From a registry of 745 patients with MacTel, patients with OFDs were characterized. All patients underwent multimodal imaging including color fundus photography, confocal blue reflectance, fundus autofluorescence, and spectral domain optical coherence tomography. Staging of eyes was done using the Gass and Blodi classification. Spectral domain optical coherence tomography characteristics in the central 1 mm of the macula in eyes with OFD are reported. RESULTS: Outer foveal defect was observed in 21 eyes of 15/745 (2%) patients with MacTel. These defects were bilateral in 6/15 (40%) patients and seen in stage 2 MacTel eyes. In order of prevalence, foveal parameters seen in OFD included hyper-reflective dots in outer retina in 19/21 (90%), ellipsoid zone loss in 18/21 (86%) eyes, interdigitation zone loss in 17/21 (81%) eyes, outer retinal hyporeflective cavitation in 14 (67%) eyes, hyporeflective cavitation at foveal pit in 8 (38%) eyes, and loss of external limiting membrane in 1 (5%) eye. The mean baseline length of the foveal ellipsoid zone loss was 240.17 ± 117.249 µm. The mean baseline central subfield thickness was 155.43 ± 17.215 µm. A total of 8/11 eyes (73%) showed an increase in size of OFD on follow-up. CONCLUSION: Outer foveal defect in MacTel eyes is characterized predominantly by foveal loss of ellipsoid zone and interdigitation zone with relative preservation of external limiting membrane.

Retrospective diagnosis of COVID-19 following the detection of central retinal artery occlusion.

Thromboembolic complications are being increasingly reported in patients with COVID-19 due to the associated hypercoagulability and are an important cause for morbidity and mortality. Retinal vascular occlusions especially arterial occlusions are one of the gravest ocular complications reported. This complication may occur in severe cases with cytokine storm or even in mild or asymptomatic patients and presentation can be anytime from few days to weeks after the onset of symptoms. Ophthalmologists should be aware of this new etiology when dealing with patients having features of retinal vascular occlusions and should investigate for the same in this pandemic situation. Although reverse transcriptase polymerase chain reaction is the diagnostic test for COVID-19, serological assays have a role in patients with delayed presentation. We describe the clinical features and multimodal imaging findings in a patient who presented with features of central retinal artery occlusion with cilioretinal artery sparing wherein his ophthalmic condition led to the diagnosis of previously undetected COVID-19 through serology. To the best of our knowledge, this is the first documentation of a case of isolated central retinal artery occlusion leading to a retrospective diagnosis of COVID-19.

Predominant peripheral lesions in patients with diabetic retinopathy and its association with systemic comorbidities.

Purpose: To determine the associations of predominant peripheral lesions (PPLs) with systemic comorbidities in individuals with diabetic retinopathy. Methods: This is a multicenter cross-sectional observational study conducted across three tertiary eye care centers in south India between January 2019 and July 2021. Ultra-widefield fundus images of consecutive patients with varying severity of diabetic retinopathy with data on systemic comorbidities were classified based on the presence or absence of PPL. Systemic comorbidities (hypertension, diabetic kidney disease, coronary artery disease, dyslipidemia, and anemia) were compared between the two groups. Results: A total of 879 participants (70.1% males) were included in the study, of which 443 (50.4%) patients had PPL. The mean age of the study participants was 56 ± 10 years, mean age of onset of diabetes was 41.24 ± 11.6 years, and mean duration of diabetes was 15.39 ± 7.6 years. The number of PPL increased with increasing severity of DR. Of all the systemic comorbidities analyzed, we found that coronary artery disease (CAD) had a significant association with PPL (Odds ratio [OR]-1.69; 95% confidence interval [CI], 1.12-2.55; P = 0.013) after adjusting for diabetic retinopathy severity, duration of diabetes, and age of onset of diabetes. Conclusion: The presence of PPL is a marker for coronary artery disease and early referral to cardiology is warranted.

Sensitivity and specificity of pseudocolor ultrawide field imaging in comparison to wide field fundus fluorescein angiography in detecting retinal neovascularization in diabetic retinopathy.

OBJECTIVE: To evaluate the diagnostic accuracy of ultrawide pseudocolor retinal photography (pseudocolor UWF) compared to wide field fundus fluorescein angiography (WFFFA) in the detection of retinal neovascularization (NV) and NV of the disc (NVD) in patients with diabetic retinopathy (DR). DESIGN: Diagnostic accuracy observational study evaluating pseudocolor UWF as the index test. The reference standard was WFFFA. SETTING: Single retinal centre in India. PARTICIPANTS: People with severe non-proliferative DR (sNPDR), early proliferative DR (ePDR) or high-risk proliferative DR (HR PDR). MAIN OUTCOME MEASURES: Sensitivity and specificity of pseudocolor UWF in the detection of NV. RESULTS: A total of 176 eyes of 94 subjects with sNPDR, ePDR or HR PDR underwent pseudocolor UWF and WFFFA. The sensitivity and specificity of pseudocolor UWF in detecting NVE were 92.5% (95% CI 86.2-96.5) and 81% (95% CI 64.8-92.0), respectively, with moderate interobserver agreement of 0.722 (p value 0.001). The positive predictive value and negative predictive value were 83.0 (71.4-90.5) and 91.5 (84.9-95.3), respectively. CONCLUSION: Compared to WFFFA as the gold standard, pseudocolor UWF has high sensitivity and specificity in detection of NV in all retinal quadrants and NVD. Therefore, pseudocolor UWF may be used as a non-invasive tool for screening and managing DR.

Microvascular changes precede visible neurodegeneration in fellow eyes of patients with asymmetric type 2 macular telangiectasia.

IMPORTANCE: Macular telangiectasia type 2 (MacTel) is bilateral disease with characteristic alterations of the macular capillary network along with decreased macular pigment in the parafoveal area. The purpose of this study was to highlight that some eyes show microvascular changes which precede any visible neuronal changes on spectral-domain optical coherence tomography (SD-OCT). METHODS: This observational study was conducted at a tertiary eye institute. From a registry of 630 patients with MacTel, we identified 4 patients with typical MacTel characteristics in only one eye with no visible changes on colour photographs or SD-OCT in the fellow eye. These 4 patients had findings of MacTel documented by colour fundus photograph, multicolour imaging (MCI), fundus autofluorescence (FAF), confocal blue reflectance (CBR), SD-OCT, and OCT-Angiography (OCT-A) in one eye. OCT-A was performed in MacTel patients using the High-resolution Spectralis (Heidelberg Engineering) module with a full-spectrum probabilistic approach and we employed a 30° x 15° (~8.8 mm × 4.4 mm) scan pattern covering the macula. MCI was done at the end so as to avoid fading the confocal blue reflectance hyperreflectivity seen in MacTel. RESULTS: On OCT-A, all 4 fellow eyes showed telangiectasia and foveal avascular zone changes in the superficial and deep capillary plexuses with no changes on SD-OCT. None of the eyes showed typically increased reflectance on CBR around the foveal area. CONCLUSION: These findings show that microvascular changes on OCT-A may occur before visible neurodegenerative changes on OCT, providing new insights into the course of the disease.

Can photoscreening effectively detect amblyogenic risk factors in children with neurodevelopmental disability?

PURPOSE: To analyze whether photoscreening can effectively detect amblyogenic risk factors in children with neurodevelopmental disability. METHODS: A prospective study of 52 children attending a special school for children with neurodevelopmental disability from December 2017 to May 2018. All were initially tested with a photoscreening device: Welch Allyn® Spot® Vision Screener: model VS100 (Spot®) and further evaluated at a later date by a pediatric ophthalmologist, with a complete ocular evaluation including squint assessment, cycloplegic retinoscopy, and dilated fundus examination. The key parameters studied were demographic features, type of neurodevelopmental disability, refraction, ocular alignment, media clarity, any other ocular morbidity, and time taken for examination. The presence of amblyogenic risk factors (ARF) was analyzed as per the 2013 guidelines of the American Association for Pediatric Ophthalmology and Strabismus. RESULTS: The mean age was 10.5 years (range: 1-17.5 years). Males (73.1%) outnumbered females (26.9%). The most common neurodevelopmental disability was cerebral palsy. Simple myopic astigmatism was the most common type of refractive error. Presence of ARF in our study was 73.1%. The sensitivity and specificity of photoscreening in detecting ARF were 96.5% and 63.61%, respectively, with a positive predictive value of 80% and negative predictive value of 92.31%. The predictive ability of photoscreening was 79.9% as per the area under curve. The average time taken for photoscreening was less than 60 s. CONCLUSION: Photoscreening can detect ARF with high sensitivity and reasonable specificity and is a handy, useful, and time-saving tool in screening children with neurodevelopmental disability.

Masson's tumor of the ocular surface - A rare clinical entity.

Masson's tumor or intravascular papillary endothelial hyperplasia (IPEH) is a benign vascular lesion usually involving the head-and-neck region. On histopathological examination, it consists of reactive proliferation of endothelial cells with papillary formations which is the key to diagnosis. This rare entity was first described in 1923 by Pierre Masson. Lesions involving orbit and eyelids have been reported before. Here, we report a case of Masson's tumor which occurred in the lid margin and later in the conjunctiva which regressed completely after excision.

Subretinal hyperreflective material morphology in neovascular age-related macular degeneration: A case control study.

Purpose: The aim of this study was to evaluate the association of morphological features of subretinal hyperreflective material (SHRM) with visual acuity (VA), geographic atrophy (GA) and scar formation in eyes with neovascular age-related macular degeneration (neovascular AMD) and to compare with controls of neovascular AMD without SHRM. Methods: Retrospective analysis of 157 wet AMD eyes with SHRM and 50 eyes without SHRM treated with Anti-VEGF. Baseline spectral domain-OCT characteristics (SHRM location, height, width, area, reflectivity, border definition) were collected and were correlated with VA at baseline, 3, 6, 12 months and looked for development of scar and geographical atrophy (GA) and were compared to the control group. Results: When compared to the control, baseline parameters with a significant predictive value of 12-VA were presence of SHRM, foveal involvement of SHRM, high reflective SHRM, well-defined SHRM borders and thick SHRM. VA was decreased with greater SHRM height, width and area (P < 0.001). Decreasing reflectivity of SHRM lesions and disappearance of SHRM correlated with better VA at 12 months (P < 0.05). At 12 months, scar and GA was present more often in eyes with persistent SHRM than in eyes with SHRM that resolved and those without SHRM in the control group. Conclusion: SHRM can be considered as a surrogate OCT biomarker in predicting final visual outcome in neovascular age-related macular degeneration. Baseline parameters predicting poorer vision at 12-follow-up were presence of SHRM involving the fovea, well-defined SHRM borders, greater SHRM height, width and area and persistence of SHRM with Anti-VEGF therapy.

Detection of Diabetic Retinopathy from Ultra-Widefield Scanning Laser Ophthalmoscope Images: A Multicenter Deep Learning Analysis.

PURPOSE: To develop a deep learning (DL) system that can detect referable diabetic retinopathy (RDR) and vision-threatening diabetic retinopathy (VTDR) from images obtained on ultra-widefield scanning laser ophthalmoscope (UWF-SLO). DESIGN: Observational, cross-sectional study. PARTICIPANTS: A total of 9392 UWF-SLO images of 1903 eyes from 1022 subjects with diabetes from Hong Kong, the United Kingdom, India, and Argentina. METHODS: All images were labeled according to the presence or absence of RDR and the presence or absence of VTDR. Labeling was performed by retina specialists from fundus examination, according to the International Clinical Diabetic Retinopathy Disease Severity Scale. Three convolutional neural networks (ResNet50) were trained with a transfer-learning procedure for assessing gradability and identifying VTDR and RDR. External validation was performed on 4 datasets spanning different geographical regions. MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (AUROC); area under the precision-recall curve (AUPRC); sensitivity, specificity, and accuracy of the DL system in gradability assessment; and detection of RDR and VTDR. RESULTS: For gradability assessment, the system achieved an AUROC of 0.923 (95% confidence interval [CI], 0.892-0.947), sensitivity of 86.5% (95% CI, 77.6-92.8), and specificity of 82.1% (95% CI, 77.3-86.2) for the primary validation dataset, and >0.82 AUROCs, >79.6% sensitivity, and >70.4% specificity for the geographical external validation datasets. For detecting RDR and VTDR, the AUROCs were 0.981 (95% CI, 0.977-0.984) and 0.966 (95% CI, 0.961-0.971), with sensitivities of 94.9% (95% CI, 92.3-97.9) and 87.2% (95% CI, 81.5-91.6), specificities of 95.1% (95% CI, 90.6-97.9) and 95.8% (95% CI, 93.3-97.6), and positive predictive values (PPVs) of 98.0% (95% CI, 96.1-99.0) and 91.1% (95% CI, 86.3-94.3) for the primary validation dataset, respectively. The AUROCs and accuracies for detecting both RDR and VTDR were >0.9% and >80%, respectively, for the geographical external validation datasets. The AUPRCs were >0.9, and sensitivities, specificities, and PPVs were >80% for the geographical external validation datasets for RDR and VTDR detection. CONCLUSIONS: The excellent performance achieved with this DL system for image quality assessment and detection of RDR and VTDR in UWF-SLO images highlights its potential as an efficient and effective diabetic retinopathy screening tool.

EARLY SPECTRAL-DOMAIN OPTICAL COHERENCE TOMOGRAPHY BIOMARKERS TO CONFIRM FELLOW EYE CHANGES IN ASYMMETRIC TYPE-2 MACULAR TELANGIECTASIA: A Case-Control Study (India Macular Telangiectasia Report 1).

PURPOSE: To evaluate the earliest spectral-domain optical coherence tomography markers in fellow eyes of asymmetric Type-2 macular telangiectasia (MacTel). METHODS: A multicentered case-control study of spectral-domain optical coherence tomography images captured on Spectralis Heidelberg Engineering, Germany, comparing features of fellow eyes of patients with asymmetric clinical presentation of MacTel with 50 age-matched control subjects. RESULTS: Of 649 patients, 28 (4.3%) with MacTel presented with asymmetric features. The mean age of the MacTel patients was 63.5 (12.4) years with female predilection (4:1). Mean best-corrected visual acuity of the unaffected eye was 0.2 logarithm of the minimum angle of resolution (20/32 Snellen equivalent). The mean central subfoveal thickness in the unaffected MacTel eyes was 194 (SD, 38) µm, and the temporal retinal thickness was 204 (SD, 43) µm. These parameters were significantly thinner than those of control subjects in whom mean central subfoveal thickness was 273 (SD, 26) µm (P = 0.001). Presence of hyperreflective outer retinal dots was found in 92.8% of the unaffected MacTel eyes. These hyperreflective dots were scattered, punctate, nonconfluent, and confined to the outer retinal layers of foveal and parafoveal region. CONCLUSION: Although these cases presented with advanced presentation of MacTel features in only one eye, temporal retinal thinning and presence of hyperreflective outer retinal dots in the fellow eye can be considered as the earliest signs of MacTel.

Lateral elongation of flat irregular pigment epithelial detachment: A novel optical coherence tomography biomarker in polypoidal choroidal vasculopathy.

Purpose: To explore novel Optical Coherence Tomography (OCT) biomarkers and precursor lesions in Polypoidal Choroidal Vasculopathy (PCV). Methods: This retrospective cohort study included 76 treatment naïve fellow eyes of PCV. Focus was given to analyse the various morphological changes in the clinically unaffected fellow retina during the follow-up period. Results: 11 fellow eyes (14.47%) developed disease activity in the form of Sub Retinal Fluid (SRF) or Intra Retinal Fluid (IRF) within a mean follow-up of 17 months. All 11 eyes (100%) showed the presence of flat irregular pigment epithelial detachment (FIPED) and a peculiar property of lateral elongation of FIPED during disease activity. A positive correlation with the disease progression was found for the same (P < 0.0001). The mean horizontal dimension of the flat irregular PED at the enrolment was 1984 ± 376u and the mean expansion of FIPED at SRF formation was 461 ± 152u. ICG taken at the time of disease activity in the fellow eye revealed branching vascular network (BVN) in 9 (81.8%) eyes, polyps in 7 (63.6%) eyes, a combination of both in 5 (45.4%) eyes. Type one BVN with interconnecting channels showed faster disease progression than type two BVN. Eye tracking ICG illustrated that BVN corresponded to the FIPED in OCT and polypoidal lesions developed at the end of expanding FIPED. Conclusion: Flat irregular pigment epithelial detachment with its characteristic property of lateral elongation may be considered as a precursor lesion for PCV and as a novel OCT biomarker for the disease activity. Fellow eyes with FIPED need close monitoring to identify development of disease activity at the earliest.