Intraocular Bioadhesives in Vitreoretinal Surgeries: A Systematic Review.

BACKGROUND: Bioadhesion is the ability of materials to adhere to biological surfaces. Bioadhesives are substances which induce or promote bioadhesion. The internal application of bioadhesives is gaining popularity in recent years and is being increasingly utilized in vitreoretinal surgeries. The aim of this review is to discuss the various bioadhesives and their applications in vitreoretinal surgeries. METHODS: PubMed, Google Scholar, ePub and Cochrane library database were used for literature selection. Keywords such as vitreoretinal surgery, bioadhesives, intraocular bioadhesives, glue, fibrin glue, cyanoacrylate glue and transforming growth factor were used individually and in differing combinations to perform a comprehensive systematic literature search. RESULTS: A total of 47 papers were retrieved and included in this review. Cyanoacrylate glue was the first bioadhesive to be utilized for vitreoretinal surgery in human eyes in 1976. The most common indications for the use of bioadhesives were in optic disc pit maculopathy, macular holes and rhegmatogenous retinal detachments. CONCLUSION: The use of intraocular bioadhesives in vitreoretinal surgery represents a significant and evolving area of interest within ophthalmic research. While the pioneering use of cyanoacrylate glue, fibrin glue and transforming growth factor beta demonstrated the possible use of intraocular adhesives, fibrin glue is the most widely used intraocular bioadhesive in vitreoretinal surgery.

Tear Protein Markers for Diabetic Retinopathy and Diabetic Macular Edema - Towards an Early Diagnosis and Better Prognosis.

BACKGROUND: Diabetic eye disease is a highly prevalent and sight-threatening disorder. It is a disease of neuro-vascular unit of the retina, if left untreated can cause blindness. Therapeutic approaches followed for its treatment can only restrict the progression of the disease with highly variable results. There is no known biomarker for an early diagonsis of this disease, therefore by the time it is detected it goes beyond repair. This creates a massive demand for development of such biomarkers that help detect disease in its earlier stages. METHODS: PUBMED (https://pubmed.ncbi.nlm.nih.gov/) was searched for articles relevant to the topic published till November 2023. The search was made using keywords such as Diabetic Retinopathy, inflammation, tear, biomarker, proteomics etc. The studies providing relevant information to prove the importance of biomarker discovery were chosen. After compiling the data, the manuscript writing was planned under relevant headings and sub-headings. RESULTS: The review provides a comprehensive overview of all the tear protein biomarker studies in the field of DR and DME. Briefly, their potential in other diseases is also elucidated. While there are many studies pertaining to DR biomarkers, the identified markers lack validations which has restricted their usage in clinics. In case of DME, there was no such study towards biomarker discovery for its diagnosis and prognosis. CONCLUSIONS: The review highlights major studies and their lacunae in the field of biomarkers discovery for DR and DME.

Suspected Retinal Toxicity After Multiple Intravitreal Ganciclovir Injections in a Patient of CMV Retinitis.

PURPOSE: Intravitreal Ganciclovir has been one of the treatments of choice for cytomegalovirus (CMV) retinitis and has been used extensively for its treatment since 1987. It has not been shown to have any major adverse effects. There are no reports on any retinal toxicity even after multiple, repeated injections. Herein, we report a rare case of retinal toxicity after multiple intravitreal injections in a patient of CMV retinitis. CASE REPORT: A 69-year-old one eyed male, who was on oral corticosteroids and systemic immunosuppression for Granulomatosis with Polyangiitis, presented with CMV retinitis in both eyes. His visual acuity was 20/60 in his right eye and no perception of light in his left eye. He was treated with multiple injections of intravitreal Ganciclovir in his right eye. The left eye was not treated since it had no vision potential. The right eye of the patient which had received multiple injections went on to developed a progressive diffuse atrophy of Retinal Pigment Epithelium (RPE). No such changes were noted in the left eye of the patient. CONCLUSION AND IMPORTANCE: We present a case of progressive diffuse RPE atrophy as a result of toxicity of intravitreal ganciclovir injections. It is important to be aware of this rare potential toxicity of intravitreal Ganciclovir.

Macular Punctate Lesions Presenting as a Primary Manifestation of Ocular Toxoplasmosis.

PURPOSE: To study clinical features and outcomes of primary ocular Toxoplasmosis (OT) cases presenting as macular punctate lesions. METHODS: Retrospective review of three cases of OT with positive Toxoplasma serology. RESULTS: We describe three cases presenting as primary OT with no evidence of old retinochoroidal scar in either eye. All the cases had multiple foveal or extrafoveal, punctate, inner/outer, or combined lesions at macula with minimal vitreous reaction. During the first/primary episode, all the lesions resolved with 1. retinal atrophy, thinning (n = 1) or 2. Progressed to limited full-thickness retinitis lesions (n = 2). Recurrence as typical retinochoroiditis was seen in one eye. More than four-fold IgG positivity was seen in all cases while IgM positivity was seen in two cases. CONCLUSIONS: Macular punctate lesions (inner/outer/combination) can be the primary manifestation of ocular toxoplasmosis in the absence of old retinochoroiditis scars in either eye.

Ten-year results of scleral-fixated intraocular lens implantation: outcomes of ab externo scleral fixation with 10-0 polypropylene suture.

PURPOSE: To describe long-term visual and anatomical outcomes of sutured scleral-fixated intraocular lens (SF IOL) implantation. SETTING: Tertiary eyecare hospital in India. DESIGN: Retrospective interventional noncomparative study. METHODS: Postoperative change in corrected distance visual acuity (CDVA) and occurrence of complications were assessed from the patient medical records. Long-term SF IOL survival rates and factors affecting the occurrence of postoperative IOL-related complications were assessed. Patients with postoperative follow-up less than 10 years or incomplete medical records were excluded. RESULTS: 64 eyes of 53 patients were included. Follow-up duration was 11.4 ± 1.2 years. Mean preoperative CDVA was 0.71 ± 0.43 logMAR (Snellen equivalent: 6/30), and mean CDVA at the final visit was 0.52 ± 0.49 logMAR (Snellen equivalent: 6/18) (P < .01). 48% cases had CDVA of 6/12 or better at the last follow-up. 58% cases had coexistent ocular pathology affecting the final visual outcome. IOL and suture-related complications were the commonest and included IOL decentration (17% cases), IOL drop (14%), and suture exposure (6%). The probability of IOL survival (postoperative period without IOL-related complications) was 90.6% at 8 years and 81.2% at 10 years (Kaplan-Meier analysis). Occurrence of postoperative IOL-related complications was unaffected by patient sex, age, indication for surgery (trauma or other), previous intraocular surgery, or technique of scleral fixation (2-point or 4-point) (multivariate regression analysis). CONCLUSIONS: Although sutured SF IOL implantation is viable with favorable long-term visual outcomes, there is a risk of postoperative IOL-related complications. Occurrence of postoperative IOL-related complications is unaffected by patient and ocular factors.

Microbiological Landscape and Epidemiology of Endophthalmitis in Children and Adolescents in a Multi-Tier Ophthalmology Network in India: An Electronic Medical Record-Driven Analytics Report.

PURPOSE: To study the epidemiology and microbiological landscape in patients (≤21 yrs) diagnosed with endophthalmitis across a multi-tier ophthalmology network in India. METHODS: This cross-sectional hospital-based study included 1,041 patients (≤21 yrs) diagnosed with endophthalmitis, between April 2012 and May 2022. The data were collected using an electronic medical record system. RESULTS: Bacteria (24%) was the most common etiology followed by fungus (2%). The majority of the patients were male (66%) with a mean age of 8.37 ± 5.99 years. The most common age group was middle childhood (6-11 years) with 365 (35.06%) patients. The patients were more commonly from the lower socio-economic status (60.81%) and urban geography (49%). The common cause of endophthalmitis was trauma (59.33%) and amongst the 279 culture positive eyes, the predominant bacteria isolated was Streptococcus pneumoniae followed by Bacillus species and fungus included predominantly Aspergillus and Candida species. The most common surgical intervention performed was intraocular antibiotics (74%) followed by pars plana vitrectomy (52%). CONCLUSION: The most common etiology of endophthalmitis in children is bacterial and traumatic in nature and presented from the lower socio-economic status. A half of the eyes warranted a vitreo-retinal surgical intervention. .

A cross-sectional study on the microbiological landscape in pediatric endophthalmitis showed that the most common cause of endophthalmitis was trauma and the predominant bacteria isolated was Streptococcus spp. and Bacillus spp. Additionally, majority of the patients were from the lower socio-economic status and urban geography and the most common surgical intervention performed was injection of intraocular antibiotics.

New Insights into HIV Life Cycle, Th1/Th2 Shift during HIV Infection and Preferential Virus Infection of Th2 Cells: Implications of Early HIV Treatment Initiation and Care.

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.

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.

Fibrin-Glue-Assisted Surgery for Idiopathic Macular Holes.

METHODS: This pilot clinical trial included 10 eyes of 10 patients with idiopathic MH, where PPV along with ILMP was done. Fibrin glue was used as a tamponade, and no postoperative positioning was given to any patient. The primary outcome measure was successful anatomical closure of the MH. The secondary outcome measures were postoperative improvement in best-corrected visual acuity (BCVA) and any complications of the procedure. RESULTS: The median age of patients was 62.5 years. Eight eyes were pseudophakic and two were phakic. The mean basal diameter of the MH was 1193 microns. The mean minimal linear diameter was 652 microns. Successful anatomic closure of MH was achieved in eight cases. The median BCVA improved from a Snellen equivalent of 20/100 preoperatively to 20/60 at 1 month postoperatively. The median follow-up period was 4 months. CONCLUSION: The findings of this study suggest that the use of fibrin glue can be useful in patients where postoperative positioning is difficult.

Bacillary layer detachment as an inflammatory biomarker in toxoplasmosis retinochoroiditis: serial evolution on optical coherence tomography.

We describe the clinical course and serial evolution of bacillary layer detachment (BALAD) on optical coherence tomography (OCT) in toxoplasmosis retinochoroiditis and its importance as an inflammatory biomarker. Colour fundus photography and swept-source OCT of the BALAD were done at the time of presentation and subsequently at 1 week, 2 weeks, 4 weeks and at 11 weeks. Treatment involved oral trimethoprim (160 mg) + sulphamethoxazole (800 mg) two times per day, started at presentation for 2 months. Oral prednisolone was started after 1 week at a dose of 50 mg a day and tapered weekly over the next 5 weeks. The BALAD initially increased after starting treatment with trimethoprim-sulphamethoxazole and regressed within 1 week after initiation of oral prednisolone. Best corrected visual acuity improved to 20/40 from 20/160 at presentation (Snellen equivalent). This suggests that BALAD is an indicator of an acute inflammatory event and the accumulated fluid is secondary to retinal and choroidal inflammation.

Effect of Age on the Etiology and Antibiotic Susceptibility Pattern of Infectious Endophthalmitis.

PURPOSE: To review the etiology and antibiotic susceptibility patterns of infectious endophthalmitis over 11 years in different age groups. METHODS: Microbiology records of culture-positive endophthalmitis cases from January 2011 and December 2021 were reviewed for the age groups 0-30, 31-60, and >60 years. Additionally, data was also analysed for trends in antibiotic susceptibility between different age groups. RESULTS: A total of 5590 patients were clinically diagnosed with endophthalmitis. Of these, 1316 (23.5%) patients were culture positive comprising of 1097 bacteria (83.3%) and 219 fungal (16.6%). Gram-positive bacteria predominated the culture-proven bacterial endophthalmitis group with 709 cases (62.6%). Streptococcus pneumoniae (9.3%) was the most prevalent organism in the age group between 0 and 30 years, while Staphylococcus epidermidis (6%) was the most prevalent organism in the age group of 31-60 years. In comparison, Pseudomonas aeruginosa (4.1%) was the most abundant organism in the age group >60 years. Interestingly, Aspergillus flavus (13.24%) was the predominant fungal pathogen in all age groups. There was an increasing trend in antibiotic resistance from younger to older age groups and this pattern was observed for almost all drugs tested except vancomycin and amikacin. CONCLUSION: While infection can occur at any age, the etiology also seems to vary. This study helps us understand the demography of endophthalmitis along with choice of empirical antibiotics that would influence treatment outcomes. Although vancomycin currently holds good for the treatment for gram-positive infections, gram-negative infections calls for an immediate need for newer drugs or advanced treatment options.

Surgical and visual outcomes after vitreoretinal surgery for complex retinal capillary hemangioblastoma.

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.

Distinct NOD2 mutations reported in three families with Blau syndrome (BS) from a single center in India - Case series and review of literature.

OBJECTIVE: Blau syndrome (BS), considered a rare pediatric autoinflammatory disease, is characterised by a triad of granulomatous arthritis, dermatitis and uveitis. Here we present a tale of three families visited in our outpatient department in the last two years (2020-2022) where more than one member was affected with either skin, ophthalmological and joint involvement with either biopsy-proven granuloma or genetic mutation at NOD2 gene suggesting the diagnosis of BS. CASE SERIES: The first family had three affected members where the mother and her two children had skin changes, polyarthritis and a pathogenic mutation in NOD2 gene (exon 4, c.1000C > T, p.Arg334Trp) suggesting BS. The second family had two affected members where both mother and her son had uveitis, skin changes with NOD2 mutation at exon 4 with c.1147G > A (p Glu 383 Lys) variant. The son also had polyarthritis and his skin biopsy was suggestive of granulomatous inflammation. In the third family with two affected members, we found a mutation in NOD2 on exon 4 (c 1324C > T, p.Lys 442 Phe) which was described as pathogenic with only one report published till date. CONCLUSION: These three cases presented to us within the last two years and led to a diagnosis of BS in three other family members with discrete mutations (commonest to rarest) on the NOD2 gene in the three families.

Comparison of the Biological Basis for Non-HIV Transmission to HIV-Exposed Seronegative Individuals, Disease Non-Progression in HIV Long-Term Non-Progressors and Elite Controllers.

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.

Medical Therapy for Large Idiopathic Full-Thickness Macular Holes.

PURPOSE: To describe the characteristics and outcomes of eyes with idiopathic full-thickness macular holes (FTMH) that underwent initial medical management. METHODS: This retrospective study included eyes with FTMH that were initially managed with one month of topical therapy. Eligible subjects were treated with dorzolamide 2% three times a day, nepafenac 0.1% twice a day, and prednisolone acetate 1% four times a day. The primary endpoints was hole closure at one month and secondary endpoint was change in best-corrected visual acuity (BCVA). RESULTS: Ten subjects (mean age: 62.80 years; female: 50%) with unilateral FTMH were studied. The mean basal diameter of the entire cohort at baseline was 824.1 µm (median 828 µm). Four (40%) of the smaller holes (mean 698 µm; median 698.50 µm) closed after one month of topical therapy, whereas larger holes (mean 908.17µm; median 889.50 µm) did not close. In one eye, the hole reopened 4 months after stopping the medication, but closed again at one month after re-starting the topical treatment. Median BCVA improved from 0.35 logMAR at baseline to 0.05 logMAR in eyes that closed but remained at 0.70 logMAR at one month in eyes that did not close. CONCLUSION: Topical corticosteroid, non-steroidal anti-inflammatory, and carbonic anhydrase inhibitor therapy may promote closure of small FTMHs, but large holes are less likely to respond. One month of topical therapy might avoid subjecting some patients to complex vitreo-retinal surgery without compromising visual outcomes. Macular hole may re-open after stopping the topical therapy.