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Purpose: To report the clinical profile and donor characteristics of post-optical keratoplasty adverse events notified at an eye bank. Methods: Between January 2013 and December 2022, 37,041 donor corneas were utilized for keratoplasty, of which 16,531 were used for penetrating keratoplasty (PK), 12,171 for endothelial keratoplasty (EK), and 1356 for anterior lamellar keratoplasty (ALK). EK included 10,956 Descemet stripping automated endothelial keratoplasty (DSAEK) and 1215 Descemet membrane endothelial keratoplasty (DMEK). The adverse events reported within the first 6 weeks of optical keratoplasty were analyzed for donor-related parameters. Results: A total of 41 (0.11%) recipients had post-keratoplasty infections. Of these, 33 occurred after EK (29 after DSAEK, and four after DMEK), two after ALK, and six after PK. The clinical presentation was keratitis alone in 16 eyes and associated with endophthalmitis in 25 eyes. The organisms isolated were gram-negative bacteria in 26 eyes, fungus in eight eyes, gram-positive bacteria in four eyes, mixed infection in five eyes, and microbiology inconclusive in seven eyes. The majority (78%) of the gram-negative infections were due to multidrug-resistant organisms. Most (88%) donor corneas were harvested from hospital premises. The most common cause of donor mortality was trauma. The median duration of presentation from surgery was 4.46 (range: 1–30) days. The death to preservation time was 4.18 (1.5–7.65) hours. The death to utilization time was 3 (2–4.7) days. Conclusion: The overall risk of infectious adverse events after keratoplasty was 0.11%, ranging from 0.08% to 0.36%. Most (80.4%) of the adverse events occurred after EK. The majority (78.9%) of the adverse events were of bacterial etiology, of which gram-negative infections (68.4%) were the most common. The trends and microbiological spectrum of organisms associated with infections should be thoroughly documented in eye banks to gain insights and formulate guidelines on the management of adverse events.

Non-infectious uveitis (NIU) encompasses a range of conditions marked by inflammation within various layers of the eye. NIU is a significant contributor to irreversible vision loss among the working-age population in developed countries. The aim of treating uveitis is to manage inflammation, prevent its recurrences and to restore or salvage vision. Presently, the standard treatment protocol for NIU involves initiating corticosteroids as the primary therapeutic agents, although more aggressive approaches and steroid sparing agent may be necessary in certain cases. These advanced treatments option include synthetic immunosuppressants like antimetabolites, calcineurin inhibitors and alkylating agents. For patients who exhibit an intolerance or resistance to corticosteroids and conventional immunosuppressive therapies, biologic agents have emerged as a promising alternative. Notably, among the biologic treatments evaluated, TNF-α inhibitors, anti-CD20 therapy and alkylating agents have shown considerable efficacy. In this review, we delve into the latest evidence surrounding the effectiveness of biologic therapy and introduce novel therapeutic strategies targeting immune components as potential avenues for advancing treatment of NIU.

Purpose: There is insufficient literature reporting the concurrent occurrence of retinal ischemic lesions with optic neuritis. In this case report, we present a distinctive instance of Optic Neuritis with a positive Myelin Oligodendrocyte glycoprotein (MOG) antibody, accompanied by retinal ischemia manifesting as paracentral acute middle maculopathy (PAMM) lesions. Observations: Our patient is a 25-year-old female who tested positive for MOG antibodies and exhibited retinal PAMM lesions without any apparent underlying ischemic cause. She received intravenous pulse steroid therapy, and her symptoms and signs completely resolved one month later. Conclusion: PAMM can serve as an initial manifestation of Myelin Oligodendrocyte glycoprotein Antibody Associated Disease (MOGAD). This case has the potential to contribute to the existing literature, facilitating a deeper exploration of the pathophysiology of retinal ischemia in MOG associated optic neuritis.

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.

PurposeNon-infectious uveitis is a complex disease characterized by intraocular inflammation of the uveal area and the leading cause of vision impairment and blindness in young people globally. However, what triggers inflammation and contributes to its recurrence remains unclear. The complement system has been linked to various immunological and inflammatory conditions. In the present study, we have systematically evaluated the role of the alternative complement pathway in the pathogenesis of non-infectious uveitis.MethodologyQuantitative PCR was done in the peripheral leukocytes to study the expression of genes and regulatory miRNA in both anterior and posterior uveitis (n=28 in each category). Multiplex ELISA was performed to measure alternative pathway complement components, such as C3b, factor B, and CFH, and aqueous humor of infectious and non-infectious uveitis patients and non-inflammatory controls (n=10 each). Western blotting was done to validate the ELISA findings in a subset of patients and controls.ResultsDownregulation of C3 and CFH mRNA in the peripheral blood was shown by quantitative PCR in the group of anterior uveiits (AU), while the opposite result was found in the group of posterior uveitis (PU). ELISA levels of C3b and CFH proteins were significantly higher in aqueous humor of infectious and non-infectious uveitis (*p = 0.03 and **p = 0.0007 respectively) as compared to the control group. Western blotting further validated (VitH) the activation of the complement cascade in the aqueous (AH) and vitreous humor of patients with non-infectious uveitis, with an increased level of C3b (n=6) and CFH (n=4) in aqueous humor. C3b level was significantly increased while CFH was reduced relative to controls in the vitreous humor (VitH) of posterior uveitis patients compared to controls (n=27 in each category). A C3b to CFH ratio was computed to assess the regulation of complement activation and this index was several folds higher in both anterior and posterior uveitis (n=10 each). The expression of miRNA-hsa-miR-146a and miRNA-hsa-miR-155-5p that regulates CFH was downregulated and nicely correlated with the increased complement proteins in both anterior and posterior uveitis (n=10 each).ConclusionOur results demonstrate a clear role of CFH and the activation of the alternative complement pathway in the pathogenesis of non-infectious uveitis; however, its therapeutic potential warrants further investigations.

Purpose: We evaluated the anatomical and functional outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma (RCH). Methods: This was a retrospective case series of 15 patients (16 eyes) with tractional or combined retinal detachment (RD) managed with pars plana vitrectomy and tumor endoresection (ER) with/without feeder vessel ligation. Results: The mean age at the time of surgery was 30 years (range, 14–46 years). The most common tumor locations were inferotemporal (six eyes) and temporal (six eyes) quadrants. Indications for surgery included exudative RD with fibrovascular proliferation (eight eyes), combined RD (five eyes), vitreous hemorrhage (four eyes), and rhegmatogenous RD (two eyes). Tumor destruction was performed with laser and/or cryotherapy in nine eyes (57%) and ER in seven eyes (43%). Feeder vessel was ligated and cauterized in 10 (63%) and six eyes (37%), respectively. Anatomical success after initial surgery was 50% (eight eyes), which improved to 88% (14 eyes) after they underwent a repeat procedure for recurrent RD (eight eyes). At the last visit, visual acuity improved in seven eyes (44%), was stable in four eyes (25%), and worsened in five eyes (31%) with a mean follow-up of 29 months (6–79 months). Comparison between the ER group and the laser/cryotherapy group revealed no significant difference in final retinal reattachment rate (89% vs. 86%, P > 0.05), with better visual outcomes in laser/cryotherapy group (57% vs. 78%, P < 0.05). Conclusion: Pars plana vitrectomy with/without tumor endoresection can be a safe and effective treatment option for complex RCHs, achieving good tumor control and anatomical success with limited functional success.

Purpose: To describe the demographics, clinical profile, and outcomes of ocular siderosis in patients presenting to a multi-tier ophthalmology hospital network in India. Methods: This cross-sectional and hospital-based study included 3,082,727 new patients who presented between August 2010 and December 2021. Patients with a clinical diagnosis of ocular siderosis in at least one eye were included. Results: Overall, 58 eyes of 57 patients (0.002%) were diagnosed with ocular siderosis. The majority were men (96.49%) and had unilateral (98.25%) affliction. The most common age group at presentation was during the third decade of life with 24 patients (42.11%). A clear history of ocular trauma was documented in 47 patients (81.03%). Major clinical signs included corneal pigment deposition in nearly half of the eyes (27/58 eyes, 46.55%), corneal scar (20/58 eyes, 34.48%), cataract (22/58 eyes, 37.93%) and retinal detachment (11/58 eyes, 18.96%). The intraocular foreign body (IOFB) was anatomically localized in a majority of the eyes (i.e., 45/58 eyes, 77.59%). The most common location of the IOFB was in the posterior segment (22/58 eyes, 37.93%). The eyes that underwent a vitreoretinal surgery with removal of IOFB had a slightly better BCVA (1.0 ± 1.01) when compared to eyes with non-removal of IOFB (1.58 ± 1.00). Conclusion: Ocular siderosis is a rare sight-threatening entity, with half of the affected eyes exhibiting severe visual impairment. Majority of the eyes in ocular siderosis will have a detectable IOFB. Surgical removal of IOFB may lead to a better visual gain when compared to non-removal.

Purpose: To describe the demographics, clinical characteristics, and presentation of solar retinopathy in patients who presented to a multi-tier ophthalmology hospital network in India. Methods: This cross-sectional, hospital-based study included 3,082,727 new patients presenting to the hospital between August 2010 and December 2021. Patients with a clinical diagnosis of solar retinopathy in at least one eye were included in the study. All the data was collected using an electronic medical record system. Results: Three hundred and forty-nine eyes of 253 (0.01%) patients were diagnosed with solar retinopathy and included in the study, and 157 patients (62.06%) had a unilateral affliction. Solar retinopathy was noted to be significantly more common in males (73.12%) and adults (98.81%). The most common age group at presentation was during the sixth decade of life with 56 (22.13%) patients. They were more commonly from the rural geography (41.9%). Among the 349 eyes, 275 (78.8%) eyes had mild or no visual impairment (20/70–20/200) found in 45 (12.89%) eyes. The most commonly associated ocular comorbidity was cataract in 48 (13.75%) eyes, followed by epiretinal membrane in 38 (10.89%) eyes. The most common retinal damage seen was interdigitation zone (IZ) disruption (38.68%), followed by inner segment–outer segment (IS–OS) disruption (33.52%). Foveal atrophy was seen in 105 (30.09%) eyes. Conclusion: Solar retinopathy is predominantly unilateral and is more common in males. It usually presents during the sixth decade of life and rarely causes significant visual impairment. The most common retinal damage seen was disruption of the outer retinal layers.

The theory of immune regulation involves a homeostatic balance between T-helper 1 (Th1) and T-helper 2 (Th2) responses. The Th1 and Th2 theories were introduced in 1986 as a result of studies in mice, whereby T-helper cell subsets were found to direct different immune response pathways. Subsequently, this hypothesis was extended to human immunity, with Th1 cells mediating cellular immunity to fight intracellular pathogens, while Th2 cells mediated humoral immunity to fight extracellular pathogens. Several disease conditions were later found to tilt the balance between Th1 and Th2 immune response pathways, including HIV infection, but the exact mechanism for the shift from Th1 to Th2 cells was poorly understood. This review provides new insights into the molecular biology of HIV, wherein the HIV life cycle is discussed in detail. Insights into the possible mechanism for the Th1 to Th2 shift during HIV infection and the preferential infection of Th2 cells during the late symptomatic stage of HIV disease are also discussed.

We report the case of a 60-year-old female with primary angle-closure glaucoma, who presented with intraocular pressure (IOP) of 0 mmHg, significant cataract, and finger-counting vision in her left eye (LE) following high-intensity focused ultrasound (HIFU) treatment. She underwent LE cataract surgery combined with pars plana vitrectomy, membrane peeling, and silicon oil injection. Postoperatively, hypotony improved, and visual acuity improved to 20/160. One and a half years later, she underwent silicone oil removal (SOR) in view of recovered ciliary secretion and elevated IOP. Post-SOR, IOP remained elevated due to complete synechial closure secondary to prolonged hypotony and the patient is awaiting an incisional surgery. This case highlights the serious vision-threatening complications of persistent hypotony following HIFU treatment. We caution the surgeons regarding the use of HIFU in eyes with good visual potential and discuss the importance of understanding the safety and efficacy of a cycloablative procedure.

Purpose: To describe the increase in prevalence of ethambutol-induced optic neuropathy (EON) in patients presenting to a single tertiary referral eye care center in India after introduction of weight-based fixed dose combinations and an increase in duration of ethambutol use from 2016 in the Revised National Tuberculosis Control Program. Methods: This was a retrospective, observational, referral hospital-based study of 156 patients with a diagnosis of EON presenting to a single tertiary referral eye care center between January 2016 and December 2019. The main outcome measure was to assess the increase in prevalence of EON cases presenting to our tertiary care institute. Results: During the 4-year study period, 156 new patients were diagnosed with EON. A total of 101 patients (64.7%) were males and 55 (35.3%) were females. The most common age group affected was 41–60 years. The significant complaint at presentation was decreased vision in all the patients. A rising trend in the number of patients diagnosed as EON was seen, with the prevalence increasing from 16 cases in 2016, 13 cases in 2017, and 31 cases in 2018 to 96 cases in 2019. Conclusion: The results of this study indicated an alarming increase in the trend of EON cases presenting to our tertiary care institute.

Purpose: To evaluate the causes of jet stream injury (JSI)-related iatrogenic retinal breaks (IRBs) during vitreoretinal surgery (VRS). Methods: The precise surgical environment, which includes the indication and type of surgical procedure, retina status, details of instrumentation and fluidic parameters, and characteristics of the jet responsible for the IRB, was noted from case records. The nature of IRB and its healing and impact on anatomical and visual outcomes were analyzed. Results: Five eyes of five patients with complete documentation of both the JSI and the IRB were included. Two cases were operated for macular hole, and one each for vitreous hemorrhage, retinal detachment, and endophthalmitis. One case had infusion-fluid-related JSI, while four developed it because of injection of surgical adjuncts (drugs, PFCL, and dye). JSI developed in two cases when the vitreous cavity was filled with fluid, while it was air-filled in three cases. In four cases, the fluid migrated into subretinal space, necessitating further maneuvers following which the breaks healed, but were directly responsible for vision loss in two cases. Conclusion: JSI related IRBs are rare but may be directly responsible for vision loss if they impact the macula. The balance between jet stream velocity, its distance from the retinal surface, the intervening media (vitreous cavity), and retinal health play an important role. It can occur because of both infusion as well as injection jets. Precautions must be taken in cases vulnerable to complications with suggested modifications in the surgical technique.

The current technique for implanting flanged intraocular lens (IOL) suffers from complications like haptic exposure and tilting of the implanted IOL. We describe a modification of the currently described technique to obviate its shortcomings. Five eyes of five patients with a minimum of 1 year of follow-up were included. In this technique, two scleral pockets were made nasal and temporal to embed the flanged haptics. The primary outcome measure was the improvement in visual acuity (VA) postoperatively and the secondary outcome measures were postoperative complications. The primary objective of this current modification is to simplify the surgical technique for secondary IOL implantation and make it more replicable and predictive. The mean age of the patients was 19.44 years. The mean preoperative VA was 0.44 logMAR which improved to 0.26 logMAR at the 6-week postoperative visit. The mean follow-up was 496+/− 80 days. The maximum follow-up was 647 days. There were no postoperative complications such as haptic exposure, hypotony, or IOL tilt in any cases. The new E-flanged IOL technique has good visual outcomes and does not have postoperative complications. It has less intraoperative manipulation and complications.

Introduction. SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome is a rare autoinflammatory condition describing the constellation of inflammatory skin, bone, and joint manifestations which result in diagnostic difficulty and therapeutic challenge. Case. Here, we present a case of a young male diagnosed with SAPHO syndrome with osteoarticular and cutaneous involvement from an early age in his life. He suffered diagnostic challenges for a long time and was hence inadequately treated. He had minimal response to conventional DMARDs but showed excellent response to TNF inhibitor (adalimumab). Later, he defaulted treatment and presented with acute anterior uveitis which was also dramatically improved with adalimumab and tofacitinib although financial constraint was always an issue for the patient. Conclusion. The uniqueness of this case was that the patient had a multiorgan involvement including osteoarticular system, skin, and eye. Both TNFi (adalimumab) and JAKinib (tofacitinib) had a good response to all organs with a net improvement in the quality of life of this patient.

Summary: The productive infection of HIV, which generates new viral progeny, depends on the activation status of the cell. In this study, we found cocaine exposure sensitizes partially active CD4+ T cells and makes them poised for productive HIV infection. We discovered that cocaine treatment enhances the metabolic state of the cells by co-stimulating several transcription factors, mainly NFAT and AP-1, the two transcription factors, which specifically play a crucial role in enhancing both HIV and the overall cellular gene expression in T cells. We found that cocaine-induced AP-1 works in tandem with NFAT to boost HIV transcription. The enhanced HIV transcription upon cocaine exposure was further confirmed through higher phosphorylation of the crucial serine residues at the carboxyl-terminal domain (CTD) of RNA polymerase II. The insights gained from this study could aid in developing highly specialized therapeutics combating the deleterious effects of cocaine on the cocaine-using HIV population.

Abstract 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.

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons who spontaneously and durably control viremia to below levels of detection for at least 12 months, even when using the most sensitive assays, such as polymerase chain reaction (PCR) in the absence of cART. Despite the fact that there is no universal agreement regarding the mechanisms by which these groups of individuals are able to control HIV infection and/or disease progression, there is a general consensus that the mechanisms of protection are multifaceted and include genetic, immunological as well as viral factors. In this review, we analyze and compare the biological factors responsible for the control of HIV in these unique groups of individuals.

Abstract 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.

Abstract Gut bacterial microbiome dysbiosis in type 2 Diabetes Mellitus (T2DM) has been reported, but such an association with Diabetic Retinopathy (DR) is not known. We explored possible link between gut bacterial microbiome dysbiosis and DR. Using fecal samples of healthy controls (HC) and people with T2DM with/without DR, gut bacterial communities were analysed using 16S rRNA gene sequencing and data analysed using QIIME and R software. Dysbiosis in the gut microbiomes, at phyla and genera level, was observed in people with T2DM and DR compared to HC. People with DR exhibited greater discrimination from HC. Microbiomes of people with T2DM and DR were also significantly different. Both DM and DR microbiomes showed a decrease in anti-inflammatory, probiotic and other bacteria that could be pathogenic, compared to HC, and the observed change was more pronounced in people with DR. This is the first report demonstrating dysbiosis in the gut microbiome (alteration in the diversity and abundance at the phyla and genera level) in people with DR compared to HC. Such studies would help in developing novel and targeted therapies to improve treatment of DR.

Optimal visualization is one of the most challenging aspects of performing vitreoretinal surgery. In situations where conventional microscopic techniques provide poor posterior visualization, the adjunctive skill set of endoscopic visualization may be needed. This allows for by-passing the opaque anterior segment media and getting access to the posterior segment pathology. Endoscopic vitrectomy is a useful and unique adjunct to microincision vitreoretinal surgery. The optical set-up of endoscopy allows for clinical approaches that are impossible with regular microscope viewing systems. These include the ability to observe across optically significant anterior segment opacities and directly visualize the posterior segment of the eye. It also allows for visualizing the difficult-to-access retroirideal, retrolental, and anterior retinal structures. Surgical access to anatomic spaces like the pars plana, pars plicata, ciliary sulcus, ciliary body, and peripheral lens is tedious. This is made simpler by endoscopy. In this review, we summarize and review the usage of the intraocular endoscope as a diagnostic and therapeutic armamentarium across a wide spectrum of ocular pathologies.

Purpose: Intraocular infection in patients with COVID-19 could be different in the presence of treatment with systemic corticosteroid and immunosuppressive agents. We describe the epidemiology and microbiological profile of intraocular infection in COVID-19 patients after their release from the hospital. Methods: We analyzed the clinical and microbiological data of laboratory-confirmed COVID-19 patients from April 2020 to January 2021 presenting with features of endogenous endophthalmitis within 12 weeks of their discharge from the hospital in two neighboring states in South India. The data included demography, systemic comorbidities, COVID-19 treatment details, time interval to visual symptoms, the microbiology of systemic and ocular findings, ophthalmic management, and outcomes. Results: The mean age of 24 patients (33 eyes) was 53.6 ± 13.5 (range: 5–72) years; 17 (70.83%) patients were male. Twenty-two (91.6%) patients had systemic comorbidities, and the median period of hospitalization for COVID-19 treatment was 14.5 ± 0.7 (range: 7–63) days. Infection was bilateral in nine patients. COVID-19 treatment included broad-spectrum systemic antibiotics (all), antiviral drugs (22, 91.66% of patients), systemic corticosteroid (21, 87.5% of patients), supplemental oxygen (18, 75% of patients), low molecular weight heparin (17, 70.8% of patients), admission in intensive care units (16, 66.6% of patients), and interleukin-6 inhibitor (tocilizumab) (14, 58.3% of patients). Five (20.8%) patients died of COVID-19-related complications during treatment for endophthalmitis; one eye progressed to pan ophthalmitis and orbital cellulitis; eight eyes regained vision >20/400. Fourteen of 19 (73.7%) vitreous biopsies were microbiologically positive (culture, PCR, and microscopy), and the majority (11 patients, 78.5%) were fungi. Conclusion: Intraocular infection in COVID-19 patients is predominantly caused by fungi. We suggest a routine eye examination be included as a standard of care of COVID-19.

Purpose: Re-emergent ocular syphilis in patients with Human immunodeficiency virus (HIV) co-infection has both diagnostic and management difficulties because of the overlapping risk factors. The clinical manifestations described in non-HIV may not be the same in patients with HIV coinfection. Immune recovery uveitis (IRU) may also alter the course of the disease causing recurrences. We studied the clinical features in correlation with CD4 counts, systemic immune status, sexual preferences and management outcomes in HIV/AIDS patients with ocular syphilis in the highly active antiretroviral treatment (HAART) era from a high endemic HIV population like India. Methods: Retrospective analysis of all patients with ocular syphilis and HIV/AIDS seen between 2016 and 2019 was done. Results: A total of 33 patients (56 eyes) with a CD4 count range of 42–612 cells/cu.mm were included. Ocular syphilis was found to be higher in individuals with high risk behavior such as men who have sex with men (MSMs) (45%). Panuveitis was the commonest manifestation (53.57%) and was even the presenting feature of HIV and syphilis in many patients. Significant vitritis, usually uncommon in HIV/AIDS immunocompromised patients was noted even with low CD4 counts in patients with ocular syphilis. Significant correlation was noted between ocular presentation and CD4 counts (P < 0.05). Conclusion: Ocular syphilis presents differently in patients with HIV/AIDS. Diffuse retinitis is seen commonly in low counts (400 cells/cu.mm). Ocular manifestations can be an indicator of the immune status of the patient. Not all patients with ocular manifestations have associated features of systemic syphilis. Ocular manifestations can be the first presentation of HIV/AIDS. Although, there is good response to systemic penicillin and HAART, recurrences and immune recovery uveitis (IRU) can also occur.

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.

There are multiple approaches to inhibit inflammatory molecules and pathways in noninfectious uveitis. The cornerstone of local and systemic anti-inflammatory treatment is corticosteroid therapy. Corticosteroids remain the most potent and efficacious drugs for treating intraocular inflammation. However, their long-term use is limited by their medium- and long-term side effects, which are a major concern. The approach taken to limit corticosteroid side effects is to introduce steroid-sparing agents that suppress the inflammatory pathways and immune response differently than corticosteroids. There are several classes of such drugs that are affordable, effective, and generally well-tolerated. Relatively recently, an increasing range of biologic agents has become available to treat intraocular inflammation. However, the relatively expensive cost of these therapies limits their use in the developing world. This systemic review aimst to discuss the use of corticosteroids and different immunosuppressive regimens in the management of various uveitides.

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.

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.

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.

We describe a case of right eye tubercular (TB) panuveitis with corneal involvement where repeated intraocular sampling was unsuccessful. Finally, evisceration and histopathology of ocular tissue confirmed the diagnosis of ocular tuberculosis. A chest X-ray showed signs of pulmonary TB. The patient was lost to follow-up but reported 2 months later with the right eyelid margin nodules with surface ulceration. Both eyelid and pulmonary lesions were resolved with anti-TB therapy.

Purpose: To study optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) features of circumscribed choroidal hemangioma (CCH) following treatment with photodynamic therapy (PDT) and transpupillary thermotherapy (TTT). Methods: A retrospective chart review of consecutive patients treated for CCH over 2 years (May 2016–April 2018). The investigations, in addition to comprehensive eye examination, included color fundus photography, B-scan ultrasonography, OCT, and OCT-A. Results: The study included 16 eyes of 16 patients (9 males and 7 females). The mean age at presentation was 43.5 ± 9 years (range 33–62 years). Macula (n = 6) and superior arcade (n = 5) were the common tumor locations. Twelve eyes received multiple treatment sessions: TTT (seven eyes; mean 2.4 sessions) and PDT (five eyes; mean 2 sessions). Four eyes were observed because vision was not threatened. Pretreatment OCT features were Bruch's membrane atrophy (15 eyes), retinal pigment epithelial atrophy (13 eyes), outer retinal abnormalities (12 eyes), and macular subretinal fluid (12 eyes). Pretreatment OCT-A features were complete loss of choriocapillaris (16 eyes), irregularly arranged fine arborizing vessels (11 eyes), and more than 50% signal void hyporeflective areas (12 eyes). Posttreatment OCT-A showed persistence of choriocapillaris loss, flat scar with fibrosis and thinning of choroid in all eyes treated with TTT, and persistence of deeper choroidal vessels and no loss of choriocapillaris in eyes treated with PDT. Conclusion: OCT and OCT-A help understand the structural outcome following PDT and TTT in circumscribed choroidal hemangioma.

Purpose: This study describes a novel surgical technique of fibrin glue-assisted retinopexy for rhegmatogenous retinal detachment (GuARD) without oil or gas tamponade after pars plana vitrectomy (PPV). Methods: This pilot clinical trial included five eyes of five patients with rhegmatogenous retinal detachments (RD). A complete PPV was done in all cases followed by fluid–air exchange, laser photocoagulation around the break/s, and application of 0.1–0.2 mL of fibrin glue. No air, long-acting gas or silicone oil was used subsequently. No specific postoperative positioning was prescribed. The primary outcome measure was efficacy of the procedure defined as successful anatomical retinal reattachment. Secondary outcome measures were postoperative improvement in best corrected visual acuity (BCVA) and complications. Results: The median age of patients was 55 (range: 36–61 years) years and median duration of symptoms was 15 (range: 7–60) days. All eyes were pseudophakic, four eyes had inferior and one eye had total RD. Successful retinal reattachment was achieved in all (100%) cases and was maintained at the end of 3–8 months of follow-up. The median BCVA improved from 20/100 preoperatively to 20/80 at 1-week and 20/50 at 1-month postoperatively. None of the eyes had any postoperative complications such as elevated intraocular pressures or unexpected inflammation. Conclusion: The findings of this study suggest that GuARD is a promising technique for treatment of rhegmatogenous RD that may allow early visual recovery while avoiding the problems of gas or oil tamponade and obviating the need of postoperative positioning.

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.

The detailed mechanisms underlying oxidative stress that leads to neuroinflammation and neurodegeneration in retinal vascular conditions, including diabetic retinopathy, retinopathy of prematurity etc., remain largely unexplored mainly due to a lack of suitable disease models that can simulate the inherent neuron–glia interactions in human retina. Specifically, establishment of a mixed retinal culture (MRC) containing both neuron and glial cell types remains a challenge due to different conditions required for their optimal growth and differentiation. Here, we establish a novel primary MRC model system containing neurons, astrocytes, Müller glia, and microglia from human donor retina that can be used to study the neuromodulatory effects of glial cells under the stress. The cell characterization based on immunostaining with individual cell type–specific markers and their presence in close vicinity to each other further underscores their utility for studying their cross talk. To the best of our knowledge, this is the first instance of an in vitro model obtained from human donor retina containing four major cell types. Next, we induce hypoxic stress to MRC to investigate if hypoxia activated neuroglia modulates altered gene expression for inflammatory, apoptotic, and angiogenic markers and Ca2+ transients by live cell imaging. Further, we performed k-means clustering of the Ca2+ responses to identify the modification of clustering pattern in stressed condition. Finally, we provide the evidence that the altered Ca2+ transient correlates to differential expression of genes shown to be involved in neuroinflammation, angiogenesis, and neurodegeneration under the hypoxic conditions as seen earlier in human cell lines and animal models of diabetic retinopathy. The major features of the hypoxic conditions in the proposed human MRC model included: increase in microglia activity, chemokine and cytokine expression, and percentage of cells having higher amplitude and frequency of Ca2+ transients. Thus, the proposed experimental system can potentially serve as an ideal in vitro model for studying the neuroinflammatory and neurodegenerative changes in the retina and identifying newer drug targets.

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.

Studies have documented dysbiosis in the gut mycobiome in people with Type 2 diabetes mellitus (T2DM). However, it is not known whether dysbiosis in the gut mycobiome of T2DM patients would be reflected in people with diabetic retinopathy (DR) and if so, is the observed mycobiome dysbiosis similar in people with T2DM and DR. Gut mycobiomes were generated from healthy controls (HC), people with T2DM and people with DR through Illumina sequencing of ITS2 region. Data were analysed using QIIME and R software. Dysbiotic changes were observed in people with T2DM and DR compared to HC at the phyla and genera level. Mycobiomes of HC, T2DM and DR could be discriminated by heat map analysis, Beta diversity analysis and LEfSE analysis. Spearman correlation of fungal genera indicated more negative correlation in HC compared to T2DM and DR mycobiomes. This study demonstrates dysbiosis in the gut mycobiomes in people with T2DM and DR compared to HC. These differences were significant both at the phyla and genera level between people with T2DM and DR as well. Such studies on mycobiomes may provide new insights and directions to identification of specific fungi associated with T2DM and DR and help developing novel therapies for Diabetes Mellitus and DR.

Drug abuse is a common comorbidity in people infected with HIV. HIV-infected individuals who abuse drugs are a key population who frequently experience suboptimal outcomes along the HIV continuum of care. A modest proportion of HIV-infected individuals develop HIV-associated neurocognitive issues, the severity of which further increases with drug abuse. Moreover, the tendency of the virus to go into latency in certain cellular reservoirs again complicates the elimination of HIV and HIV-associated illnesses. Antiretroviral therapy (ART) successfully decreased the overall viral load in infected people, yet it does not effectively eliminate the virus from all latent reservoirs. Although ART increased the life expectancy of infected individuals, it showed inconsistent improvement in CNS functioning, thus decreasing the quality of life. Research efforts have been dedicated to identifying common mechanisms through which HIV and drug abuse lead to neurotoxicity and CNS dysfunction. Therefore, in order to develop an effective treatment regimen to treat neurocognitive and related symptoms in HIV-infected patients, it is crucial to understand the involved mechanisms of neurotoxicity. Eventually, those mechanisms could lead the way to design and develop novel therapeutic strategies addressing both CNS HIV reservoir and illicit drug use by HIV patients.

The central nervous system (CNS) is highly compartmentalized and serves as a specific site of human immunodeficiency virus (HIV) infection. Therefore, an understanding of the cellular populations that are infected by HIV or that harbor latent HIV proviruses is imperative in the attempts to address cure strategies, taking into account that HIV infection and latency in the CNS may differ considerably from those in the periphery. HIV replication in the CNS is reported to persist despite prolonged combination antiretroviral therapy due to the inability of the current antiretroviral drugs to penetrate and cross the blood–brain barrier. Consequently, as a result of sustained HIV replication in the CNS even in the face of combination antiretroviral therapy, there is a high incidence of HIV-associated neurocognitive disorders (HAND). This article, therefore, provides a comprehensive review of HIV transcriptional regulation, latency, and therapy in the CNS.

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the male genital tract and explain how and why circumcised men are more protected from HIV infection during sexual activity than uncircumcised men who are at higher risk of HIV acquisition.

In 2020, the global prevalence of human immunodeficiency virus (HIV) infection was estimated to be 38 million, and a total of 690,000 people died from acquired immunodeficiency syndrome (AIDS)–related complications. Notably, around 12.6 million people living with HIIV/AIDS did not have access to life-saving treatment. The advent of the highly active antiretroviral therapy (HAART) in the mid-1990s remarkably enhanced the life expectancy of people living with HIV/AIDS as a result of improved immune functions. However, HAART has several drawbacks, especially when it is not used properly, including a high risk for the development of drug resistance, as well as undesirable side effects such as lipodystrophy and endocrine dysfunctions, which result in HAART intolerability. HAART is also not curative. Furthermore, new HIV infections continue to occur globally at a high rate, with an estimated 1.7 million new infections occurring in 2018 alone. Therefore, there is still an urgent need for an affordable, effective, and readily available preventive vaccine against HIV/AIDS. Despite this urgent need, however, progress toward an effective HIV vaccine has been modest over the last four decades. Reasons for this slow progress are mainly associated with the unique aspects of HIV itself and its ability to rapidly mutate, targeting immune cells and escape host immune responses. Several approaches to an HIV vaccine have been undertaken. However, this review will mainly discuss progress made, including the pre-clinical and clinical trials involving vector-based HIV DNA vaccines and the use of integrating lentiviral vectors in HIV vaccine development. We concluded by recommending particularly the use of integrase-defective lentiviral vectors, owing to their safety profiles, as one of the promising vectors in HIV DNA vaccine strategies both for prophylactic and therapeutic HIV vaccines.

A 33-year-old male underwent an optical keratoplasty elsewhere in the right eye following which he developed endophthalmitis and subsequently underwent a pars plana vitrectomy and lensectomy. At presentation, he had a deep stromal crystalline infiltration along the graft–host junction. A large therapeutic keratoplasty was performed, and the excised corneal button was evaluated. Histopathology revealed gram-positive round-to-oval budding structures and microbiology identified the organism as Candida glabrata. He was treated with antifungals in the postoperative period. At 4 months after therapeutic keratoplasty, the patient developed recurrent endophthalmitis, following stoppage of antifungals. The treatment was reinstituted for another year, and the patient did well with a clear graft at 18-month-follow-up period after the recurrence episode. Management of infectious crystalline keratopathy with endophthalmitis is a challenging situation and requires long-term treatment.

The persistence of latent HIV provirus pools in different resting CD4+ cell subsets remains the greatest obstacle in the current efforts to treat and cure HIV infection. Recent efforts to purge out latently infected memory CD4+ T-cells using latency-reversing agents have failed in clinical trials. This review discusses the epigenetic and non-epigenetic mechanisms of HIV latency control, major limitations of the current approaches of using latency-reversing agents to reactivate HIV latency in resting CD4+ T-cells, and potential solutions to these limitations.

The purpose of the study was to review the current evidence and design a diabetic macular edema (DME) management guideline specific for India. The published DME guidelines from different organizations and publications were weighed against the practice trends in India. This included the recently approved drugs. DME management consisted of control of diabetes and other associated systemic conditions, such as hypertension and hyperlipidemia, and specific therapy to reduce macular edema. Quantification of macular edema is precisely made with the optical coherence tomography and treatment options include retinal laser, intravitreal anti-vascular endothelial growth factors (VEGF), and implantable dexamethasone. Specific use of these modalities depends on the presenting vision and extent of macular involvement. Invariable eyes with center-involving macular edema benefit from intravitreal anti-VEGF or dexamethasone implant therapy, and eyes with macular edema not involving the macula center benefit from retinal laser. The results are illustrated with adequate case studies and frequently asked questions. This guideline prepared on the current published evidence is meant as a guideline for the treating physicians.

The C-promoter binding factor-1 (CBF-1) is a potent and specific inhibitor of the human immunodeficiency virus (HIV)-1 LTR promoter. Here, we demonstrate that the knockdown of endogenous CBF-1 in latently infected primary CD4+ T cells, using specific small hairpin RNAs (shRNA), resulted in the reactivation of latent HIV proviruses. Chromatin immunoprecipitation (ChIP) assays using latently infected primary T cells and Jurkat T-cell lines demonstrated that CBF-1 induces the establishment and maintenance of HIV latency by recruiting polycomb group (PcG/PRC) corepressor complexes or polycomb repressive complexes 1 and 2 (PRC1 and PRC2). Knockdown of CBF-1 resulted in the dissociation of PRCs corepressor complexes enhancing the recruitment of RNA polymerase II (RNAP II) at HIV LTR. Knockdown of certain components of PRC1 and PRC2 also led to the reactivation of latent proviruses. Similarly, the treatment of latently infected primary CD4+ T cells with the PRC2/EZH2 inhibitor, 3-deazaneplanocin A (DZNep), led to their reactivation.

Human immunodeficiency virus type-1 (HIV-1) can either undergo a lytic pathway to cause productive systemic infections or enter a latent state in which the integrated provirus remains transcriptionally silent for decades. The ability to latently infect T-cells enables HIV-1 to establish persistent infections in resting memory CD4+ T-lymphocytes which become reactivated following the disruption or cessation of intensive drug therapy. The maintenance of viral latency occurs through epigenetic and non-epigenetic mechanisms. Epigenetic mechanisms of HIV latency regulation involve the deacetylation and methylation of histone proteins within nucleosome 1 (nuc-1) at the viral long terminal repeats (LTR) such that the inhibition of histone deacetyltransferase and histone lysine methyltransferase activities, respectively, reactivates HIV from latency. Non-epigenetic mechanisms involve the nuclear restriction of critical cellular transcription factors such as nuclear factor-kappa beta (NF-κB) or nuclear factor of activated T-cells (NFAT) which activate transcription from the viral LTR, limiting the nuclear levels of the viral transcription transactivator protein Tat and its cellular co-factor positive transcription elongation factor b (P-TEFb), which together regulate HIV transcriptional elongation. In this article, we review how T-cell receptor (TCR) activation efficiently induces NF-κB, NFAT, and activator protein 1 (AP-1) transcription factors through multiple signal pathways and how these factors efficiently regulate HIV LTR transcription through the non-epigenetic mechanism. We further discuss how elongation factor P-TEFb, induced through an extracellular signal-regulated kinase (ERK)-dependent mechanism, regulates HIV transcriptional elongation before new Tat is synthesized and the role of AP-1 in the modulation of HIV transcriptional elongation through functional synergy with NF-κB. Furthermore, we discuss how TCR signaling induces critical post-translational modifications of the cyclin-dependent kinase 9 (CDK9) subunit of P-TEFb which enhances interactions between P-TEFb and the viral Tat protein and the resultant enhancement of HIV transcriptional elongation.

Fibrocellular membrane or epiretinal membrane (ERM) forms on the surface of the inner limiting membrane (ILM) in the inner retina and alters the structure and function of the retina. ERM formation is frequently observed in ocular inflammatory conditions, such as proliferative diabetic retinopathy (PDR) and retinal detachment (RD). Although peeling of the ERM is used as a surgical intervention, it can inadvertently distort the retina. Our goal is to design alternative strategies to tackle ERMs. As a first step, we sought to determine the composition of the ERMs by identifying the constituent cell-types and gene expression signature in patient samples. Using ultrastructural microscopy and immunofluorescence analyses, we found activated microglia, astrocytes, and Müller glia in the ERMs from PDR and RD patients. Moreover, oxidative stress and inflammation associated gene expression was significantly higher in the RD and PDR membranes as compared to the macular hole samples, which are not associated with inflammation. We specifically detected differential expression of hypoxia inducible factor 1-α (HIF1-α), proinflammatory cytokines, and Notch, Wnt, and ERK signaling pathway-associated genes in the RD and PDR samples. Taken together, our results provide new information to potentially develop methods to tackle ERM formation.

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.

Extracellular vesicles (EVs) play an important role in intercellular communication. They are naturally released from cells into the extracellular environment. Based on their biogenesis, release pathways, size, content, and function, EVs are classified into exosomes, microvesicles (MVs), and apoptotic bodies (ApoBDs). Previous research has documented that EVs, specifically exosomes and MVs, play an important role in HIV infection, either by promoting HIV infection and pathogenesis or by inhibiting HIV-1 to a certain extent. We have also previously reported that EVs (particularly exosomes) from vaginal fluids inhibit HIV at the post-entry step (i.e., reverse transcription, integration). Besides the role that EVs play in HIV, they are also known to regulate the process of wound healing by regulating both the immune and inflammatory responses. It is noted that during the advanced stages of HIV infection, patients are at greater risk of wound-healing and wound-related complications. Despite ongoing research, the data on the actual effects of EVs in HIV infection and wound healing are still premature. This review aimed to update the current knowledge about the roles of EVs in regulating HIV pathogenesis and wound healing. Additionally, we highlighted several avenues of EV involvement in the process of wound healing, including coagulation, inflammation, proliferation, and extracellular matrix remodeling. Understanding the role of EVs in HIV infection and wound healing could significantly contribute to the development of new and potent antiviral therapeutic strategies and approaches to resolve impaired wounds in HIV patients.