Relationship between macular perfusion and lesion distribution in diabetic retinopathy.

BACKGROUND/OBJECTIVES: To assess the relationship between macular vessel density metrics and foveal avascular zone (FAZ) characteristics on optical coherence tomography angiography (OCTA) and lesion distribution in eyes with diabetic retinopathy (DR). SUBJECTS/METHODS: Patients with DR who underwent both Optos ultrawidefield (UWF) pseudocolor imaging and macular OCTA (Cirrus Angioplex, 6 × 6 mm) were included in this cross-sectional observational study. The distribution of DR lesions was assessed by comparing each of the peripheral ETDRS extended fields (3-7) against their corresponding ETDRS field, hence eyes were defined as either having predominantly peripheral lesions (PPL) or predominantly central lesions (PCL). En face OCTA images from the superficial and deep capillary plexuses (SCP and DCP) were then analysed using Image J software. Perfusion density (PD), vessel length density (VLD), and fractal dimensions (FD) were calculated following binarization and skeletonization of the images. RESULTS: Out of 344 eyes, 116 (33.72%) eyes had PPL and 228 (66.28%) eyes had PCL. For all DRSS levels, VLD, PD, and FD were not significantly different between eyes with PPL and PCL. The FAZ in eyes with PPL, however, was found to be more circular in shape compared to eyes with PCL (p = 0.037). CONCLUSION: Although the presence of PPL has been associated with a higher risk for diabetic retinopathy progression, the macular perfusion is similar in eyes with PPL and PCL. The FAZ is more circular in eyes with PPL, but the clinical relevance of this difference remains to be defined.

VKH disease in the elderly: Variations in clinical course as compared to VKH disease in adults.

PURPOSE: To describe disease characteristics and outcomes of Vogt-Koyanagi-Harada (VKH) disease in elderly patients. METHODS: Retrospective analysis of patients older than 50 years with VKH disease at two referral centers in India. Demographics, extraocular and ocular involvement, treatment, complications, and visual acuity outcomes were noted. RESULTS: In total, 69 patients (mean age at presentation: 56.4 ± 4.7 years) were analyzed; 6/69 patients had diabetes mellitus at presentation, and 10/69 had hypertension. Clinical signs included anterior chamber cells >2+ (29%), granulomatous keratic precipitates (23%), disc hyperemia (26%), neurosensory retinal detachment (34.7%), and "sunset-glow" fundus (52.1%). Patients were classified as probable (n = 50, 72.4%), incomplete (n = 18, 26%), and complete VKH (n = 1, 1.4%). The mean follow-up period was 20.2 ± 19.4 months. Improvement in mean BCVA of (0.63 LogMAR, 6 Snellen lines) was noted on the last follow-up. Patients receiving systemic steroids with immunosuppressants ( P < 0.0001) had better visual outcomes at final follow-up compared to steroids alone ( P = 0.103). Eight patients (11.6%) had complications due to systemic immunosuppressants, and 17 patients (24.6%) developed diabetes mellitus or had worsening of diabetes while on systemic corticosteroids. CONCLUSION: Few patients presented with systemic manifestations in our cohort. Those treated with steroids and concurrent immunosuppressants had better outcomes. However, therapy with immunosuppressants was encountered with major dose-limiting complications in a significant number of elderly patients with VKH syndrome.

LV Prasad Eye Institute EyeSmart electronic medical record-based analytics of big data: LEAD-Uveitis Report 1: Demographics and clinical features of uveitis in a multi-tier hospital based network in Southern India.

Purpose: To describe the demographics and epidemiology of uveitis presenting to a multi-tier ophthalmology hospital network in Southern India. Methods: Cross-sectional hospital-based study of 19,352 patients with uveitis presenting between March 2012 and August 2018. Results: In total, 1,734,272 new patients were seen across the secondary and tertiary centers of our multi-tier ophthalmology hospital network during the study period. Among them, 25,353 eyes of 19,352 patients were diagnosed with uveitis and were included in the study. Uveitis constituted 1.11% of all cases. The majority of patients were male (60.33%) and had unilateral (68.09%) affliction. The most common age group was 21-50 years with 12,204 (63.06%) patients. The most common type of uveitis was anterior uveitis, which was seen in 7380 (38.14%) patients, followed by posterior uveitis in 5397 (23.89%) patients. Among the infectious causes, tuberculosis was the most common etiology (2551 patients, 13%) followed by toxoplasmosis (1147 patients, 6%). Conclusion: Uveitis constituted 1.11% of all cases presenting to our clinics. It was more common in the age group of 21-50 and was predominantly unilateral. Anterior uveitis was the most common subtype seen in 38%.

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.

Vogt Koyanagi Harada Disease In Paediatric Age Group: Clinical Characteristics, Remission, Recurrences and Complications in Asian Indian Population.

PURPOSE: To describe disease characteristics and outcomes of Vogt-Koyanagi-Harada (VKH) syndrome in paediatric patients. STUDY DESIGN: Retrospective chart analysis. METHODS: A RETROSPECTIVE: Analysis of all patients ≤16 years with VKH syndrome was done. Clinical presentations, complications, recurrences and outcomes in cases of paediatric VKH were reviewed. RESULTS: 72 eyes of 36 patients with a mean age at presentation of 13.7 ± 2.34 years were assessed. Mean duration of symptoms and follow up were 9.88 ± 17.3 weeks and 55 months respectively. Clinical signs at presentation included anterior chamber cells >2+(34/72eyes, 47.2%), granulomatous keratic precipitates (6 eyes, 8.3%), posterior synechiae (35 eyes,48.6%), disc edema (46 eyes, 63.8%), neurosensory retinal detachments (44 eyes, 61.1%) and 'sunset-glow' fundus (9 eyes, 12.5%). Best corrected visual acuity (BCVA) at the time of presentation was 1.3logMAR or a Snellens equivalent of 20/400 which improved to 0.51logMAR (Snellens equivalent of 20/63) at last follow up. Remission was achieved in 61.1% cases. More than half of our patients developed one or more complications. CONCLUSION: VKH in paediatric patients poses a challenge due to a delayed presentation and paediatric VKH patients have a worse visual acuity at the time of presentation as compared to adult age groups. Rates of remission may be low along with high risk of complications and hence there is a need for prolonged immunosuppression.

CLOSTRIDIAL ENDOPHTHALMITIS: CLINICAL PRESENTATIONS, MANAGEMENT OUTCOMES, AND REVIEW OF LITERATURE.

PURPOSE: To describe the clinical presentations, diagnosis and management outcomes of clostridial endophthalmitis, and a review of the previous literature. DESIGN: Retrospective, interventional case series from January 2005 to March 2018 and a literature review. METHODS: The study included seven eyes of seven patients with culture-proven Clostridium sp. endophthalmitis. Identification of Clostridium sp. was confirmed by the VITEK 2 system using the ANC card. When VITEK failed to identify the organism, MALDI-TOF was used. Data regarding demography, clinical presentations, interventions received, and final visual and anatomical outcomes were noted. RESULTSTHE: mean age of the patients was 28.28 ± 22.35 years (median 21 years). By the etiology of infection, 5 (75%) eyes were post-open-globe injury, 1 (12.5%) was post-trabeculectomy, and 1 (12.5%) was postintravitreal injection. The mean follow-up was 9.71 ± 12.03 months, median 6 months. Two samples were positive for Clostridium perfringens, one each for C. subterminale, C. difficile, and C. tertium, and two were unidentified clostridial species. Favorable anatomical outcome was seen in 3/7 eyes (42.85%). Favorable functional outcome was seen in 2/7 eyes (28.57%). These were comparable with the outcomes of the pooled pre-existing literature. There was a trend toward better functional and anatomical outcomes and lesser evisceration/enucleation rates with vitrectomy instead of a vitreous tap, although not statistically significant. All cases showed susceptibility to empirically used intravitreal antibiotic vancomycin. CONCLUSION: Commonest setting of clostridial endophthalmitis is post-open-globe injury. Despite treatment with appropriate antibiotics, the visual and anatomical outcome is unsatisfactory because of high organism virulence. Early vitrectomy may allow for globe salvage and potential vision.

Endoscopy-assisted pars plana lensectomy for brunescent cataracts in eyes with microcornea with microphthalmos.

PURPOSE: Conventional cataract surgeries can be a challenge in eyes with microcorneas due to difficult manipulation in a crowded anterior chamber (AC) and can lead to a high occurrence of corneal edema and an increased rate of complications. Similarly, in cases of dense brunescent cataracts even a lensectomy through posterior approach may prove to be difficult because of inadequate visualization. An endoscopyassisted pars plana lensectomy can help in obviating these difficulties. This study aims to describe the surgical technique of endoscopy-assisted pars plana lensectomy in eyes with brunescent cataract, microcornea, and microphthalmos. METHODS: Retrospective review of two cases where endoscopy-assisted pars plana vitrectomy and lensectomy was performed for patients with dense cataract and microcornea and microphthalmos. RESULT: Complete clearance of the cataract was achieved without having to resort to a sclerocorneal incision. Postoperatively the cornea was clear and there was no postoperative corneal edema. CONCLUSION: Endoscopy-assisted pars plana lensectomy can help in overcoming the challenges of conventional anterior and posterior approaches of cataract extraction in cases of microcornea with reduced intraoperative and postoperative complications.

Intraocular Viral Communities Associated With Post-fever Retinitis.

The virome of ocular fluids is naive. The results of this study highlight the virome in the vitreous fluid of the eye of individuals without any ocular infection and compare it with the virome of the vitreous fluid of individuals with retinitis. A total of 1,016,037 viral reads were generated from 25 vitreous fluid samples comprising control and post-fever retinitis (PFR) samples. The top 10 viral families in the vitreous fluids comprised of Myoviridae, Siphoviridae, Phycodnaviridae, Herpesviridae, Poxviridae, Iridoviridae, Podoviridae, Retroviridae, Baculoviridae, and Flaviviridae. Principal coordinate analysis and heat map analysis clearly discriminated the virome of the vitreous fluid of the controls from that of the PFR virome. The abundance of 10 viral genera increased significantly in the vitreous fluid virome of the post-fever retinitis group compared with the control group. Genus Lymphocryptovirus, comprising the human pathogen Epstein-Barr virus (EBV) that is also implicated in ocular infections was significantly abundant in eight out of the nine vitreous fluid viromes of post-fever retinitis group samples compared with the control viromes. Human viruses, such as Hepacivirus, Circovirus, and Kobuvirus, were also significantly increased in abundance in the vitreous fluid viromes of post-fever retinitis group samples compared with the control viromes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analysis and the network analysis depicted an increase in the immune response by the host in the post-fever retinitis group compared with the control group. All together, the results of the study indicate changes in the virome in the vitreous fluid of patients with the post-fever retinitis group compared to the control group.

Cytomegalovirus retinitis in patients of non-Hodgkin's lymphoma: clinical presentations and outcomes.

BACKGROUND: Cytomegalovirus (CMV) retinitis in patients with Non-Hodgkin's Lymphoma (NHL) can occur even in the presence of high CD 4 counts and can behave differently when compared to CMV retinitis in human immunodeficiency (HIV) patients. It, therefore, becomes important to understand its varied presentations and the challenges in management of these cases. The aim of this study was to analyse the various patterns of presentations and outcomes of CMV Retinitis in patients with NHL. STUDY DESIGN: A retrospective chart review of seven eyes of four patients of NHL presenting with CMV retinitis between June 2017 and May 2020 was done. METHODS: Clinical patterns of CMV Retinitis, CD4 counts at the time of presentation and the duration of treatment along with recurrences and time for recurrence of retinitis were assessed. RESULTS: Granular or indolent retinitis (6 out of 7 eyes) was the commonest form of CMV retinitis in patients of NHL. Three patients had a presenting CD4 count above 150 cells/mm3 and none of them were below 50 cells/mm3. Floaters were the commonest presenting complaint. All patients had vitritis and majority of the patients (3 out of 4) had anterior chamber (AC) inflammation. Two out of the 4 patients had a recurrence (mean time 33.8 days) after stopping the maintenance phase of ganciclovir and one patient had significant myelosuppression related to oral valganciclovir which required discontinuation of the drug. CONCLUSION: CMV retinitis in NHL patients is usually of an indolent or granular type and can occur even in the presence of high CD4 counts as compared to patients with HIV. These patients may require a long term maintenance in view of frequent recurrences after discontinuation of treatment.

Topiramate induced bilateral hypopyon uveitis and choroidal detachment: a report of two cases and review of literature.

BACKGROUND: Topiramate (TPM) is a drug commonly used by neurophysicians and psychiatrists for a plethora of indications. Topiramate has been reported to induce acute angle closure glaucoma as an adverse effect. However, there is limited literature on Topiramate causing hypopyon uveitis and intense ocular inflammation. It is imperative for ophthalmologists as well as physicians to be aware of the potential sight threatening ocular adverse effects of Topiramate. We report 2 rare consecutive cases of severe hypopyon uveitis and choroidal detachments after using Topiramate. CASE PRESENTATION: Two patients presented with sudden onset of angle closure, bilateral hypopyon uveitis and choroidal detachments. On reassessing a detailed treatment history, it was found that both patient were taking oral Topiramate which had been started 2 weeks before the onset of ocular symptoms. The bilateral hypopyon and angle closure were considered to be induced by Topiramate and the drug was discontinued. The patients were started on oral and topical steroids which led to resolution of hypopyon uveitis and choroidal detachments. The visual acuity improved and the intraocular pressure also got normalised in both the cases. CONCLUSIONS: Topiramate can lead to a bilateral hypopyon uveitis and severe ocular inflammation. An urgent cessation of topiramate along with topical and systemic steroids is required to prevent serious complications.

LncRNA VEAL2 regulates PRKCB2 to modulate endothelial permeability in diabetic retinopathy.

Long non-coding RNAs (lncRNAs) are emerging as key regulators of endothelial cell function. Here, we investigated the role of a novel vascular endothelial-associated lncRNA (VEAL2) in regulating endothelial permeability. Precise editing of veal2 loci in zebrafish (veal2gib005Δ8/+ ) induced cranial hemorrhage. In vitro and in vivo studies revealed that veal2 competes with diacylglycerol for interaction with protein kinase C beta-b (Prkcbb) and regulates its kinase activity. Using PRKCB2 as bait, we identified functional ortholog of veal2 in humans from HUVECs and named it as VEAL2. Overexpression and knockdown of VEAL2 affected tubulogenesis and permeability in HUVECs. VEAL2 was differentially expressed in choroid tissue in eye and blood from patients with diabetic retinopathy, a disease where PRKCB2 is known to be hyperactivated. Further, VEAL2 could rescue the effects of PRKCB2-mediated turnover of endothelial junctional proteins thus reducing hyperpermeability in hyperglycemic HUVEC model of diabetic retinopathy. Based on evidence from zebrafish and hyperglycemic HUVEC models and diabetic retinopathy patients, we report a hitherto unknown VEAL2 lncRNA-mediated regulation of PRKCB2, for modulating junctional dynamics and maintenance of endothelial permeability.

Endoscopic visualization-assisted corneal bee sting removal.

Purpose: Deeply embedded corneal foreign bodies and intrastromal foreign body removal can often be a challenge. The aim of this report was to describe the utility of endoscopy in visualization and removal of an embedded corneal bee stinger. Methods: A 44-year-old male patient developed toxic keratopathy after injury from a bee stinger. On examination, the bee stinger was noted to be deeply embedded in the corneal stroma. A superficial keratectomy was initially attempted; however, the stinger was noted to be intrastromal and protruding into the anterior chamber and could not be removed. An Endoscopy-assisted visualization was used to remove the stinger. Results: The bee stinger was successfully removed and the patient's vision improved to 20/100 from an initial CFCF (counting fingers close to face) at time of presentation. At the end of 3 months follow-up, there was residual corneal edema along with cataractous changes in the lens as a sequelae of the initial bee sting injury. The patient subsequently underwent an endothelial keratoplasty along with phacoemulsification with intraocular lens implantation and the final BCVA improved to 20/40. Conclusion: Endoscopyassisted visualisation of anterior chamber and angle structures can be valuable in removal of retained and deeply embedded corneal or intracameral foreign bodies.

Presumed Natural History of Combined Hamartoma of the Retina and Retinal Pigment Epithelium.

PURPOSE: To correlate structural changes of combined hamartoma of the retina and retinal pigment epithelium (CHRRPE) with patient age. DESIGN: Retrospective study. PARTICIPANTS: Fifty eyes of 49 patients (age range, 1-74 years) with CHRRPE studied at 9 tertiary vitreoretinal institutions. METHODS: We analyzed the clinical findings with respect to lesion topography and pigmentation as well as investigated the OCT findings regarding the thickness, vitreoretinal interface, outer plexiform layer distortion, ellipsoid zone disruption, and retinal pigment epithelium-Bruch's membrane complex involvement of CHRRPE. MAIN OUTCOME MEASURES: Clinical and imaging findings of CHRRPE at different ages. RESULTS: Analysis of 50 CHRRPE patients revealed that younger patients were more likely to demonstrate partial thickness involvement of the retina (P = 0.009) with predominantly inner retinal layer involvement (P = 0.04). The inverse was true for older patients with CHRRPE. In addition, older patients more commonly showed pigmentary changes. Eyes with CHRRPE were more likely to show an increase in central macular thickness independently of tumor location. CONCLUSIONS: Based on these findings, we believe that CHRRPE typically begins in the inner retina and continues toward the outer retina over time, with increase in central macular thickness, despite the location of the tumor.

Mycobiome changes in the vitreous of post fever retinitis patients.

Fungi have been associated with various diseases of the eye like keratitis, uveitis and endophthalmitis. Despite this fact, fungal microbiome (mycobiome) studies compared to the bacterial microbiome studies have remained neglected. In the present study, using metagenomic sequencing, the mycobiomes of the vitreous of healthy control individuals (VC, n = 15) and individuals with post fever retinitis + non-PFR uveitis (PFR+, n = 9) were analysed and compared. The results indicated that Ascomycota was the most predominant phylum in both VC and PFR+ groups. Further, at the genera level it was observed that the abundance of 17 fungal genera were significantly different in post fever retinitis (PFR, n = 6) group compared to control group. Of these 17 genera, it was observed that 14 genera were relatively more abundant in PFR group and the remaining 3 genera in the VC group. Genus Saccharomyces, a commensal of the gut and skin, was predominantly present in the vitreous of both the cohorts, however it was significantly less abundant in PFR group. Further, significant increase in the genera that have a pathogenic interaction with the host were observed in PFR group. On the whole the mycobiome in both the groups differed significantly and formed two distinct clusters in the heatmap and Principal co-ordinate analysis. These results demonstrate significant changes in the mycobiome from the vitreous of post fever retinitis patients compared to healthy controls thus implying that dysbiotic changes in the fungal vitreous microbiome are associated with PFR.

Clinical manifestations and outcomes of ocular syphilis in Asian Indian population: Analysis of cases presenting to a tertiary referral center.

PURPOSE: To describe disease manifestations and outcomes of ocular syphilis in Asian Indian population. METHODS: Retrospective analysis of patients diagnosed with ocular syphilis at a tertiary referral center in India. Demographics, history, extraocular and ocular manifestations, ocular and systemic investigations, treatment and visual acuity outcomes were noted. All patients were diagnosed after necessary laboratory investigations including HIV ELISA (Human immunodeficiency virus, enzyme-linked immunosorbent assay), VDRL (venereal disease research laboratory), and TPHA (treponema pallidum hemagglutination). RESULTS: Totally, 20 patients with mean age at presentation 38.25 ± 9.76 were analyzed. 9/20 patients had bilateral involvement. 8/20 had concurrent HIV at presentation with an average CD4 counts of 592.25 ± 411.34 cells/microliter. The mean duration of symptoms at time of presentation was 15.45 ± 35.15 weeks. VDRL test was reactive in 45% (9/20) patients whereas, all patients had a reactive TPHA test. Clinical manifestations included outer retinal placoid chorioretinitis lesions (8/20, 40%), followed by retinitis mimicking acute retinal necrosis as the second most common phenotype (4/20, 20%). Other presenting manifestations noted were panuveitis, miliary retinitis lesions, retinal vasculitis, intermediate uveitis, and anterior uveitis. The clinical phenotypes in immunocompromised included panuveitis, acute retinal necrosis and isolated anterior uveitis. Mean follow up duration was 6.32 ± 6.15 months. An improvement in mean best corrected visual acuity (BCVA) of (0.63 LogMAR, approximately 6 Snellen lines, P < 0.02) was noted at last follow-up. CONCLUSION: Phenotypic manifestations of ocular syphilis are varied. Non-treponemal tests like VDRL may be unreliable when compared with treponemal tests in diagnosing ocular syphilis. Syphilitic uveitis is considered equivalent to neurosyphilis and is treated similar to neurosyphilis.

Endophthalmitis with opaque cornea managed with primary endoscopic vitrectomy and secondary keratoplasty: Presentations and outcomes.

Purpose: To describe the outcomes of endophthalmitis with opaque cornea managed with primary endoscopic vitrectomy and secondary keratoplasty. Methods: Retrospective consecutive interventional case series. All cases of endophthalmitis with opaque cornea which underwent endoscopic vitrectomy followed by secondary keratoplasty were analyzed. The study period was from Jan 2015 to March 2019. The outcome measures were resolution of infection, the magnitude of unnecessary keratoplasties avoided and corneal graft survival. The final anatomic and functional outcomes were reported and compared with relevant literature. Results: Seventy-eight eyes of 78 patients underwent endoscopic pars plana vitrectomy for endophthalmitis with the opaque cornea, of these 14 eyes of 14 patients were deemed eligible for further corneal intervention and were included in the study. The mean age at presentation was 42.27 ± 21.6 years (median 36 years). Etiology-wise, eight cases (57.14%) were post-trauma, three cases (21.42%) post-keratoplasty, two cases (14.28%) were endogenous, and one case (7.14%) following corneal dermoid excision and wound melt. Culture positivity was in 5/14 (35.71%). The mean interval between endoscopic vitrectomy and keratoplasty was 5.42 ± 2.69 months (median 3.5 months). The mean follow-up noted was 20.42 ± 11.45 months (median 17.5 months). The infection resolved in 100% of cases. Unnecessary keratoplasties were avoided in 64/78 (82%) cases due to the primary endoscopic intervention. The favorable anatomic outcome was seen in 11/14 (78.57%) of cases and favorable functional outcome in 8/14 (57.14%) cases. Conclusion: Endoscopic vitrectomy allows for early intervention in endophthalmitis with the opaque cornea. This facilitates early settlement of infection, globe preservation, greater graft survival, and lesser repeat posterior segment procedures.

Comparison of the Vitreous Fluid Bacterial Microbiomes between Individuals with Post Fever Retinitis and Healthy Controls.

Ocular microbiome research has gained momentum in the recent past and has provided new insights into health and disease conditions. However, studies on sight threatening intraocular inflammatory diseases have remained untouched. In the present study, we attempted to identify the bacterial microbiome associated with post fever retinitis using a metagenomic sequencing approach. For this purpose, bacterial ocular microbiomes were generated from vitreous samples collected from control individuals (VC, n = 19) and individuals with post fever retinitis (PFR, n = 9), and analysed. The results revealed 18 discriminative genera in the microbiomes of the two cohorts out of which 16 genera were enriched in VC and the remaining two in PFR group. These discriminative genera were inferred to have antimicrobial, anti-inflammatory, and probiotic function. Only two pathogenic bacteria were differentially abundant in 20% of the PFR samples. PCoA and heatmap analysis showed that the vitreous microbiomes of VC and PFR formed two distinct clusters indicating dysbiosis in the vitreous bacterial microbiomes. Functional assignments and network analysis also revealed that the vitreous bacterial microbiomes in the control group exhibited more evenness in the bacterial diversity and several bacteria had antimicrobial function compared to the PFR group.

A Systematic Investigation on Complement Pathway Activation in Diabetic Retinopathy.

The complement system plays a crucial role in retinal homeostasis. While the proteomic analysis of ocular tissues in diabetic retinopathy (DR) has shown the deposition of complement proteins, their exact role in the pathogenesis of DR is yet unclear. We performed a detailed investigation of the role of the complement system by evaluating the levels of major complement proteins including C3, C1q, C4b, Complement Factor B (CFB), and Complement Factor H (CFH) and their activated fragments from both the classical and alternative pathways in vitreous humor and serum samples from proliferative DR (PDR) patients and controls. Further, the expressions of complements and several other key pro- and anti-angiogenic genes in the serum and vitreous humor were analyzed in the blood samples of PDR and non-PDR (NPDR) patients along with controls without diabetes. We also assessed the pro-inflammatory cytokines and matrix metalloproteinases in the vitreous humor samples. There was a significant increase in C3 and its activated fragment C3bα' (110 kDa) along with a corresponding upregulation of CFH in the vitreous of PDR patients, which confirmed the increased activation of the alternative complement pathway in PDR. Likewise, a significant upregulation of angiogenic genes and downregulation of anti-angiogenic genes was seen in PDR and NPDR cases. Increased MMP9 activity and upregulation of inflammatory markers IL8 and sPECAM with a downregulation of anti-inflammatory marker IL-10 in PDR vitreous indicated the possible involvement of microglia in DR pathogenesis. Further, a significantly high C3 deposition in the capillary wall along with thickening of basement membranes and co-localization of CFH expression with CD11b+ve activated microglial cells in diabetic retina suggested microglia as a source of CFH in diabetic retina. The increased CFH levels could be a feedback mechanism for arresting excessive complement activation in DR eyes. A gradual increase of CFH and CD11b expression in retina with early to late changes in epiretinal membranes of DR patients indicated a major role for the alternative complement pathway in disease progression.

Distribution of peripheral lesions identified by mydriatic ultra-wide field fundus imaging in diabetic retinopathy.

PURPOSE: To analyze the distribution of diabetic retinopathy (DR) lesions in an Indian population using ultra-wide field (UWF) fundus imaging. METHODS: Seven hundred fifteen subjects (1406 eyes) with diabetic retinopathy in India were enrolled in this multicenter, prospective, observational study using UWF pseudocolor imaging with Optos Daytona Plus (Optos plc, Dunfermline, Scotland, UK). Images were transmitted to Doheny Image Reading Center, Los Angeles, CA, for grading. The ETDRS grid was overlaid on stereographic projections of UWF images, and images were graded independently by 2 masked graders. Lesion distribution was graded as predominantly central (PCL) or predominantly peripheral (PPL) according to previous criteria, considering both lesion number and area. An image was graded as PPL if > 50% of the lesion area was seen in at least one peripheral field as compared with the corresponding ETDRS field. Diabetic retinopathy severity was also assessed based on the International Classification of Diabetic Retinopathy (ICDR) grading scale. The main outcome measures were lesion distribution (PPL versus PCL): overall and within specific fields in eyes with various grades of DR. RESULTS: Lesion distribution was rated to be PPL in 37% of eyes and PCL in 63% of eyes (P < 0.003). The frequency of a PPL distribution varied significantly across all ICDR severity levels, with frequencies of mild non-proliferative DR (NPDR) (30.9%), moderate NPDR (40.3%), severe NPDR (38.5%) and PDR (34.9%), P = 0.005. When assessing which individual fields were rated to show a PPL distribution, the frequency was greatest in field 4 and least in field 7. For any grade of DR, temporal fields showed the greatest PPL frequency, followed in order by the superior, inferior, and nasal fields (P < 0.001). Only 3.5% of eyes showed PPL distribution in all five peripheral fields. CONCLUSIONS: One-third of the UWF images showed a PPL distribution in this cohort with the temporal quadrant having the widest distribution of PPL. As the PPL distribution varied significantly between various grades of DR, UWF imaging may prove to be important for screening of referral warranted retinopathy.

Aspergillus Endophthalmitis: Clinical Presentations and Factors Determining Outcomes.

PURPOSE: The aim of this study was to describe the clinical presentations, management and factors determining outcomes of Aspergillus endophthalmitis. DESIGN: Retrospective, interventional, multicentric case series. METHODS: The study included 91 eyes of 91 patients with culture-proven Aspergillus endophthalmitis. Anterior chamber fluid and/or vitreous and/or intraocular lens were submitted for microbiological evaluation in all cases. The data analysis included patient demography, clinical presentations, interventions, and final treatment outcomes. The main outcome measures were the final visual acuity and the globe salvation. The factors determining better visual and/or anatomical outcomes were analyzed. RESULTS: The mean age of the patients was 39.71 ±â€Š20.16 years (median 40 years, range 3-76 years). By etiology, the primary event before the endophthalmitis was trauma (42; 46.15%) eyes, cataract surgery (acute-onset: 30; 32.96% and delayed-onset: 6; 6.59%) eyes, endogenous (10; 10.98%) eyes, and cornea surgery (3; 3.29%) eyes. The mean follow up was 5.78 ±â€Š6.74 months (median 3, range 0.5-40 months). The odds of a favorable visual outcome were presenting vision > hand motions [odds ratio (OR) = 3.33, P = 0.02], absence of corneal infiltrate (OR = 5.4, P = 0.03), vitrectomy instead of a vitreous tap only (OR = 4.26, P = 0.03), administration of intravitreal voriconazole (OR = 3.63, P = 0.02), and absence of fungal elements on primary microscopy (OR = 3.42, P = 0.02). CONCLUSIONS: Early vitrectomy and intravitreal voriconazole yielded better anatomic and functional outcomes in Aspergillus endophthalmitis. Favorable visual outcome was achieved in a fifth of the eyes and globe was salvaged in two-thirds of the eyes.