Ophthalmologic profile of patients with systemic sclerosis.

PURPOSE: To study the ophthalmologic manifestations of systemic sclerosis (SSc) and its correlation with autoantibody profile. METHODS: A cross-sectional study on 200 eyes of 100 consecutive adult patients diagnosed with SSc was performed at a tertiary care center in Northern India. The examination of ocular adnexa, anterior segment, and posterior segment with slit-lamp biomicroscopy, tear film break-up time (TBUT), Schirmer's II test, and choroidal thickness measurement by swept-source ocular coherence tomography was done. Autoantibody profile was available for 85 patients, and its statistical association with the ocular examination findings was analyzed. RESULTS: In total, 100 patients (93 females and 7 males) were included. The mean age was 45.11 ± 11.68 years, and the mean disease duration was 6.93 ± 3.68 years. Meibomian gland disease was more commonly found in patients with the diffuse subtype of SSc (P = 0.037). Choroidal thickness was increased in 34% and decreased in 7% (reference range = 307 ± 79 mm) patients. Reduced TBUT, meibomian gland dysfunction, and eyelid stiffness had a statistically significant association with the presence of anti-Scl-70 antibody (P = 0.003, <0.0001, and 0.004, respectively). These patients had ocular fatigue, foreign body sensation, and burning sensation. No significant association was noted with the presence of SS-A/Ro and SS-B/La antibodies. CONCLUSION: This study highlights the need for an active comprehensive ophthalmic evaluation. Approximately 75% of the patients in our cohort had ocular involvement to varying extent. An isolated presence of anti-Scl70 antibody was also found to have a positive association with dry eye disease.

Central Retinal Artery Occlusion With Cilioretinal Artery Sparing.

This case report describes a diagnosis of central retinal artery occlusion in a patient in their early 30s who presented with decreased vision in the left eye for 1 week.

Cycle threshold values of SARS-CoV-2 RNA in conjunctival swabs and nasopharyngeal secretions: a comparative study from a tertiary care center in India.

PURPOSE: To detect the viral RNA load of SARS-CoV-2 in conjunctival swabs of COVID-19 patients, and compare with nasopharyngeal swabs. METHODS: Conjunctival swabs of COVID-19 patients (with PCR positive nasopharyngeal swabs) were subjected to quantitative reverse transcription-polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2 RNA. The cycle threshold (Ct) values of Open Reading Frame 1 (ORF 1 Ab gene) and nucleoprotein (N gene) PCRs were used to assess the viral RNA load, and compare them with the baseline values of nasopharyngeal swabs. RESULTS: Of 93 patients, 17 (18.27%) demonstrated SARS-CoV-2 RNA in conjunctival swabs. Baseline nasopharyngeal swabs were collected at a median of 2 days; while, the conjunctival swabs were collected at median 7 days, from onset of illness (p < 0.001). Despite a significant delay in conjunctival swab collection than nasopharyngeal swabs, the Ct values (ORF or N gene PCRs) were comparable between nasopharyngeal swab and conjunctival swab samples. Subsequently, during the recovery period, in four of these 17 patients (with conjunctival swab positivity), when the second nasopharyngeal swab was 'negative', the conjunctival swab was 'positive'. CONCLUSION: The conjunctival swabs demonstrated SARS-CoV-2 RNA in 17 (18.27%) of 93 COVID-19 patients. Our results may suggest a delayed or a prolonged shedding of the virus/viral RNA on the ocular surface than in nasopharyngeal mucosa.

Predicting visual outcomes following anti-vascular endothelial growth factor treatment for diabetic macular edema.

PURPOSE: To assess the utility of pre-defined imaging biomarkers on optical coherence tomography (OCT) and OCT angiography (OCTA) in patients with diabetic macular edema (DME) following anti-vascular endothelial growth factor (anti-VEGF) therapy in determining visual and anatomical outcomes. METHODS: In this prospective, non-randomized, and interventional study, 17 patients with treatment-naive DME were included. OCT biomarkers [size/reflectivity of cysts, disorganization of retinal inner layers, integrity of ellipsoid zone or external limiting membrane, subfoveal serous retinal detachment, hyper-reflective foci (HRF)] and OCTA [vascular density (VD), foveal avascular zone (FAZ), and total micro-aneurysms in superficial capillary plexus and deep capillary plexus (DCP)] were analyzed at baseline and after three monthly intravitreal anti-VEGF injections. Response was defined as a decrease of 10% or more in central macular thickness from the baseline after three injections. RESULTS: 13/17 (76.47%) patients were categorized as responders to anti-VEGF therapy. Non-responders had significantly greater hyper-reflectivity of cysts (P = 0.015), larger cystic spaces (P = 0.023), and an increased number of HRF (P = 0.04) at baseline. On OCTA, non-responders showed larger FAZ in DCP (1.35 ± 0.21 versus 1.14 ± 0.28 mm2) (P = 0.042) and lower VD (61.17 ± 0.45 versus 62.73 ± 3.32) in DCP at baseline. At 3 months, the VD increased in responders (63.10 ± 3.42) compared to a decrease in non-responders (60.82 ± 1.13) (P = 0.032). CONCLUSIONS: Non-responders show a higher number of micro-aneurysms, larger FAZ, and lower VD in the DCP on OCTA and higher cyst hyper-reflectivity and HRF and larger cystic spaces on OCT imaging.

Optical Coherence Tomography and Optical Coherence Tomography Angiography in Neglected Diseases.

A group of self-limiting and frequently neglected diseases exist in the literature like Rickettsial disease, Malaria, Dengue fever, Chikungunya, West Nile virus infection, Rift Valley fever, Bartonellosis, or Lyme disease which are poorly understood due to lack of proper diagnostic testing. Currently, multimodal imaging has become a critical modality in the diagnosis and management of ocular diseases. Optical coherence tomography (OCT) is one such remarkable imaging modality in the field of ophthalmology providing high-resolution, cross-sectional images of the retina and choroid with the recent advances such as enhanced depth imaging and swept source OCT. Additionally, OCT angiography (OCTA) has further revolutionised dynamic imaging of retinal and choroidal vasculature non-invasively. This review article highlights the OCT and OCTA biomarkers in the diagnosis and prognosis of the aforementioned neglected diseases.

Retrolental Bullous Retinal Detachment as the Presenting Feature of Vogt-Koyanagi-Harada Disease in an Elderly Indian Female: Diagnostic and Therapeutic Challenge.

PURPOSE: To report an atypical case of Vogt-Koyanagi-Harada (VKH) disease with retrolental bullous retinal detachment (RD). METHODS: A case report. CASE: A 67-year-old Indian woman with bilateral, gradual visual loss presented with both eyes light perception, keratic precipitates, 2+ cells and bullous RD, which was retrolental in right eye (RE). Systemic investigations were unremarkable. She received systemic corticosteroids, and underwent pars plana vitrectomy (PPV) in left eye (LE). Intraoperatively, sunset glow with leopard-spot fundus were suggestive of VKH disease. Immunosuppressive therapy was added. At 2 years, vision was 3/60 in RE and 6/36 in LE. The LE retina reattached immediately following surgery, while RE exudative RD resolved very gradually following corticosteroids. SUMMARY: This report illustrates diagnostic as well as therapeutic challenge in VKH disease presenting with retrolental bullous RD. PPV provided a faster anatomical and functional restoration than systemic corticosteroid therapy alone, which has potential adverse effects in the elderly.

Vitreous hemorrhage - Causes, diagnosis, and management.

Vitreous hemorrhage is associated with a myriad of conditions such as proliferative diabetic retinopathy, proliferative retinopathy following vascular occlusion and vasculitis, trauma, retinal breaks, and posterior vitreous detachment without retinal break. Multiple pathological mechanisms are associated with development of vitreous hemorrhage such as disruption of abnormal vessels, normal vessels, and extension of blood from an adjacent source. The diagnosis of vitreous hemorrhage requires a thorough history taking and clinical examination including investigations such as ultra-sonography, which help decide the appropriate time for intervention. The prognosis of vitreous hemorrhage depends on the underlying cause. Treatment options include observation, laser photo-coagulation, cryotherapy, intravitreal injections of anti-vascular endothelial growth factor, and surgery. Pars plana vitrectomy remains the cornerstone of management. Complications of vitreous hemorrhage include glaucoma (ghost cell glaucoma, hemosiderotic glaucoma), proliferative vitreoretinopathy, and hemosiderosis bulbi.

Pathogenesis of Bacterial Uveitis.

PURPOSE: To describe the pathogenesis and the general immune mechanisms of the most frequent causes of bacterial uveitis. METHODOLOGY: Narrative review. RESULTS: Both extra- and intracellular bacteria can induce uveitis, whereas intracellular bacteria are generally transported into the inner eye via cells of the innate immune system, mainly macrophages. Systemic adaptive immunity is usually induced before the bacteria are localized to the inner eye, and once T and B cells have detected the pathogens behind the blood-eye barriers they elicit an acute and/or chronic inflammatory response deteriorating visual acuity that can severely affect the non-regenerating, intraocular tissues. CONCLUSIONS: An understanding of pathogenic mechanisms, and its correlation with clinical and imaging features, can facilitate early recognition of microbial factors and institution of appropriate therapy.

Subretinal Hyperreflective Material (SHRM) as biomarker of activity in Exudative and Non- exudative inflammatory choroidal neovascularization.

AIM: To analyze the structural features and therapeutic response in clinical and subclinical inflammatory choroidal neovascularization (i-CNV) detected inside subretinal hyperreflective material (SHRM) using swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography (SS-OCTA). METHODS: In this prospective interventional study, subjects with quiescent posterior uveitis presenting with SHRM on SS-OCT and CNV network on SS-OCTA were included. Subjects with intraretinal fluid/subretinal fluid (IRF/SRF) received intravitreal antivascular endothelial growth factor (anti-VEGF) injections, while those with no IRF/SRF either received treatment or observation for 6 months until they developed IRF/SRF or decrease in best-corrected visual acuity (BCVA)/metamorphopsia. Serial comparisons included SHRM width and height and intrinsic flow signal on OCTA. RESULTS: 28 eyes of 22 subjects (12 males; mean age: 29.52 ± 12.56 years) were evaluated. Subjects with IRF/SRF at baseline (n = 6 eyes; termed as exudative iCNVs) receiving treatment showed significant improvement in BCVA (p = .017), SHRM width/height and flow signal (p < .05). Among eyes with no IRF/SRF (n = 22; termed as non-exudative iCNVs), 7 received treatment and showed significant improvement in SHRM parameters and BCVA (p < .05). 4/15(26.67%) eyes that received no treatment developed IRF/SRF upon 6-month follow-up. CONCLUSION: SHRM may act as a useful biomarker to monitor activity and response to therapy in eyes with iCNV.

Recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination.

PURPOSE: To report recurrence of tubercular choroiditis following anti-SARS-CoV-2 vaccination in two patients with quiescent disease activity for more than a year. METHODS: Retrospective observational case reports. RESULTS: Two patients (one female and one male) under follow-up for posterior uveitis having stable course with absence of ocular inflammation for more than a year presented with recurrence of choroiditis lesions 2-6 weeks following anti-SARS-CoV-2 vaccination. Both the patients were managed with intravitreal dexamethasone implant (Ozurdex®, Allergan, Inc., Irvine, CA, USA) and showed resolution of choroiditis lesions upon follow-up. CONCLUSIONS: Acute onset recurrence of inflammation, in absence of any change in health status or treatment suggests the potential role of vaccination being the trigger of this reactivation. Given large-scale vaccination against novel coronavirus- SARS-CoV-2, careful vigilance is warranted to pick up the disease recurrence in patients with posterior uveitis.

Tubercular serpiginous choroiditis.

Tubercular association with serpiginous choroiditis, also called 'serpiginous-like choroiditis' or 'multifocal serpiginoid choroiditis' (MSC) is reported from world over, especially from endemic countries. Though the exact mechanism is not yet clear, a direct or indirect infectious trigger by Mycobacterium tuberculosis (MTB) is believed to cause choroiditis.The link of immune mechanisms with ocular inflammation caused by MTB is emerging, and has been supported by both experimental and human data. The molecular and histopathological findings of tubercular serpiginous-like choroiditis have been demonstrated in clinicopathological reports, as well as in animal models. Young to middle-aged healthy males are more frequently affected. The choroiditis lesions of tubercular serpiginous-like choroiditis evolve as multifocal lesions, affecting the retinal periphery as well as posterior pole. They begin as discrete lesions, and spread in a serpiginoid pattern to become confluent. Fundus imaging including autofluorescence is extremely helpful in monitoring patients for response to therapy. Its diagnosis is essentially clinical. Corroborative evidence is obtained by a positive tuberculin skin test, or a positive QuantiFERON-TB Gold (Cellestis, Carnegie, Victoria, Australia) test, and/or radiological (chest X-ray or chest CT scan) evidence of TB elsewhere in the body. Systemic corticosteroids are the mainstay of therapy to control active inflammation, while ATT helps to reduce recurrence of inflammatory attacks. Immunosuppressive agents are indicated in cases with relentless progression, paradoxical worsening, or recurrent choroiditis.

Meningoencephalitis in primary antibody deficiency: Our experience from northwest India.

BACKGROUND/OBJECTIVES: Patients with primary antibody deficiency (PAD) are predisposed to develop meningoencephalitis, often considered to be enteroviral. However, there is a paucity of literature on this subject, and there are no studies from developing countries. METHODS: We analyzed our cohort of children with PAD who developed meningoencephalitis. RESULTS: This complication was observed in 13/135 (10.4%) patients with PAD - 5 patients had X-linked agammaglobulinemia (XLA), 7 had common variable immunodeficiency (CVID) and 1 had suspected nuclear factor kappa B essential modulator (NEMO) defect. Mean age at onset of neurological illness was 9.3 years. Presenting features included seizures (n=8), neurodevelopmental delay (n=2), regression of milestones (n=2), and acute flaccid paralysis (n=1). Trough IgG levels were found to be low in 12/13 patients at the time of development of neurological symptoms. Herpes simplex virus (HSV), cytomegalovirus (CMV), and Streptococcus pneumoniae were isolated in 1 each. Eight (72.7%) patients had altered signal hyperintensities in gray matter and deep white matter on magnetic resonance imaging (MRI), while 4 patients showed global cerebral atrophy. All patients were treated with high-dose intravenous immunoglobulin (IVIg). Fluoxetine was given to 3 patients. Eight patients in the present series have died, 3 have recovered with varying degrees of neurological sequelae and 2 patients are showing gradual recovery. CONCLUSIONS: To conclude, meningoencephalitis is an uncommon complication in patients with PAD and is associated with high morbidity and mortality. Early diagnosis of immune deficiency and initiation of replacement immunoglobulin therapy may prevent the development of neurological complications.

Morphological characterization of subretinal hyper-reflective material in posterior uveitis using swept-source optical coherence tomography and optical coherence tomography angiography.

Purpose: To analyze the structural features of subretinal hyper-reflective material (SHRM) in posterior uveitis using swept-source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (SS-OCTA). Methods: In this observational study, subjects with quiescent posterior uveitis and the presence of SHRM on SS-OCT were subjected to SS-OCTA to identify the presence of an intrinsic choroidal neovascular (CNV) network. OCT features were compared for SHRM harboring CNV (vascular SHRM) with those without CNV network (avascular SHRM) to identify clinical signs pointing toward the presence of CNVM inside SHRM. Results: Forty-two eyes of 33 subjects (18 males; mean age: 29.52 ± 12.56 years) were evaluated. Two-thirds (28/42) of eyes having SHRM on SS-OCT harbored intrinsic neovascular network (vascular SHRM). Increased reflectivity of SHRM (P < 0.001) and increased transmission of OCT signal underlying SHRM (P = 0.03) were suggestive of the absence of CNVM. The presence of intra/subretinal fluid (P = 0.08) and pitchfork sign (P = 0.017) were important markers of vascular SHRM. Conclusion: SHRM is an important OCT finding in eyes with posterior uveitis. Meticulous assessment of SHRM characteristics on SS-OCT can aid in identifying the underlying intrinsic neovascular network.

MULTICOLOR CONFOCAL SCANNING LASER OPHTHALMOSCOPE IMAGING IN POSTERIOR UVEITIS.

PURPOSE: To study the utility of MultiColor confocal scanning laser ophthalmoscope imaging (MCI) in identifying the morphology of uveitic lesions compared with conventional color fundus photography (CFP) in patients with posterior uveitis. METHODS: In this prospective observational study, subjects with posterior uveitis underwent MCI and CFP. The images obtained by the two modalities were analyzed by two independent reviewers for vitreoretinal surface abnormalities, retinal fluid and hemorrhages, and depth/location of lesions. These findings were compared with the clinical findings and other imaging techniques. RESULTS: Sixty-nine eyes of 43 patients (25 men) with mean age of 33.5 ± 13.9 years were studied. MultiColor imaging had better sensitivity and specificity in detecting vitreoretinal interface abnormalities, such as epiretinal membrane and inner retinal striae, compared with CFP. MultiColor imaging failed to detect retinochoroiditis lesions in 5 of 6 eyes (83%) and choroiditis in 9 46 eyes (20%), which were detected on CFP and clinical examination. Also, MCI showed a high false-positive rate of 34% in detecting intraretinal hemorrhages. CONCLUSION: Retinochoroidal lesions in posterior uveitis may be poorly identified on MCI compared with CFP and clinical examination. One must exercise caution in commenting on disease morphology based on MCI alone.

Redrawing vitreoretinal surgical training program in the COVID-19 era: Experiences of a tertiary care institute in North India.

Purpose: The COVID-19 pandemic has brought medical and surgical training to a standstill across the medical sub-specialties. Closure of outpatient services and postponement of elective surgical procedures have dried up opportunities for training vitreoretinal trainees across the country. This "loss" has adversely impacted trainees' morale and mental health, leading to feelings of uncertainty and anxiety. Therefore, there is an urgent need to redraw the surgical training program. We aimed to describe a systematic stepwise approach to vitreoretinal surgical training. Methods: We introduced a three-pronged approach to vitreoretinal surgical training comprising learn from home, wet lab and simulator training, and hands-on transfer of surgical skills in the operating room in our institute. Results: Encouraging results were obtained as evaluated by feedback from the trainees about the usefulness of this three-pronged approach in developing surgical skills and building their confidence. Conclusion: The disruption caused by the COVID-19 global pandemic should be used as an opportunity to evolve and reformulate surgical training programs to produce competent vitreoretinal surgeons of the future.

The use of optical coherence tomography angiography in comparing choriocapillaris recovery between two treatment strategies for multifocal choroiditis: a pilot clinical trial.

PURPOSE: To compare differences in choriocapillaris flow deficit (CC FD) in multifocal choroiditis (MFC) between two treatment arms using optical coherence tomography angiography (OCTA). METHODS: In this prospective randomized clinical trial, patients were randomized to either Group 1 which received standard tapering dose of oral corticosteroids, or Group 2 which received additional dexamethasone implant (or intravitreal methotrexate). The patients were followed-up until 12 weeks using OCTA and other imaging tools. CC FD and visual acuity between the two groups were compared at each visit. RESULTS: Twenty-five subjects (17 males; 25 eyes) were studied (11 eyes in Group 1). There were no differences between the visual acuity or CC FD (1.12 versus 1.08 mm2; p = 0.86) at baseline between the groups. However, patients in Group 2 achieved better visual acuity (0.32 ± 0.23 versus 0.15 ± 0.11; p = 0.025) and CC FD (0.54 versus 0.15 mm2; p = 0.008) at 12 weeks. CONCLUSIONS: OCTA is a useful tool in monitoring the CC FD recovery after treatment in MFC. Patients receiving intravitreal corticosteroid/methotrexate in addition to systemic corticosteroid showed greater resolution of CC FD on OCTA compared to those receiving only oral corticosteroids.

Automated lesion segmentation and quantification for prediction of paradoxical worsening in patients with tubercular serpiginous-like choroiditis.

To develop and evaluate a fully automated pipeline that analyzes color fundus images in patients with tubercular serpiginous-like choroiditis (TB SLC) for prediction of paradoxical worsening (PW). In this retrospective study, patients with TB SLC with a follow-up of 9 months after initiation of anti-tubercular therapy were included. A fully automated custom-designed pipeline was developed which was initially tested using 12 baseline color fundus photographs for assessment of repeatability. After confirming reliability using Bland-Altman plots and intraclass correlation coefficient (ICC), the pipeline was deployed for all patients. The images were preprocessed to exclude the optic nerve from the fundus photo using a single-shot trainable WEKA segmentation algorithm. Two automatic thresholding algorithms were applied, and quantitative metrics were generated. These metrics were compared between PW + and PW- groups using non-parametric tests. A logistic regression model was used to predict probability of PW for assessing binary classification performance and receiver operator curves were generated to choose a sensitivity-optimized threshold. The study included 139 patients (139 eyes; 92 males and 47 females; mean age: 44.8 ± 11.3 years) with TB SLC. Pilot analysis of 12 images showed an excellent ICC for measuring the mean area, intensity, and integrated pixel intensity (all ICC > 0.89). The PW + group had significantly higher mean lesion area (p = 0.0152), mean pixel intensity (p = 0.0181), and integrated pixel intensity (p < 0.0001) compared to the PW- group. Using a sensitivity optimized threshold cut-off for mean pixel intensity, an area under the curve of 0.87 was achieved (sensitivity: 96.80% and specificity: 72.09%). Automated calculation of lesion metrics such as mean pixel intensity and segmented area in TB SLC is a novel approach with good repeatability in predicting PW during the follow-up.