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.

Retinopathy of prematurity in triplets - Indian twin city ROP study report number 12.

PURPOSE: To evaluate the incidence and severity of retinopathy of prematurity (ROP) amongst surviving triplets. METHODS: Records of preterm babies born to mothers with triplet pregnancies were retrieved from our Indian twin city ROP study database between 1 Jan 2000 and 31 Dec 2020 and analyzed. RESULTS: 253 surviving triplet babies born to 108 mothers were evaluated. 48 out of 108 (44%) mothers received treatment for infertility. Data was available and analyzed for 242 babies (484 eyes). Mean gestational age was 31.76 ± 3.74 weeks (26- 38 weeks). The mean birth weight was 1.44 ± 0.37 kg (0.57-2.76 kg). At the first screening, incomplete vascularization was noted in 67% (131 babies;322 eyes) of which ROP was diagnosed in 14% (28 babies; 56 eyes). Among them, only 18 babies (53%) were the smallest birth weight babies in each of the triplet sets. Treatment with laser or bevacizumab was performed in 14 babies (5.8%), one eye of one baby additionally needed vitreoretinal surgical intervention. Good anatomical outcomes in terms of regression of ROP without sequelae were achieved in all babies. CONCLUSION: The present study reveals low incidence and favorable outcomes of ROP in triplet pregnancies in a large cohort of babies from a middle-income country. Our cohort did not show any difference in the treatment-requiring ROP among the larger or smaller birth weight babies of the same gestational age. In multiple pregnancies, gestational age remains a critical factor for ROP development; however, this does not necessitate modifying screening or treatment criteria in such triplet pregnancies.

Antibiotic susceptibility in Endophthalmitis Management Study and intravitreal antibiotic practice trend in India-EMS Report #5.

AIM: Analyze antibiotic susceptibility in the Endophthalmitis Management Study (EMS) and compare it with the current intravitreal antibiotic practice trend of members of the Vitreoretinal Society of India (VRSI) practicing in India. METHODS: The microbiology work-up of undiluted vitreous included microscopy, culture-susceptibility, polymerase chain reaction (PCR), and next-generation sequencing (NGS). VRSI members were invited to the survey. The EMS conventional culture-susceptibility (PCR and NGS excluded) results were compared vis-a-vis gram-positive cocci (GPC), gram-negative bacilli (GNB), and less commonly used antibiotics with the current recommended intravitreal antibiotics. p < 0.05 was considered significant. RESULTS: Culture and positivity (culture + PCR/NGS) positivity was 28.8% and 56.1%, respectively. GPC was most susceptible to cefazolin, linezolid, and vancomycin; GNB was most susceptible to amikacin, ceftazidime, colistin, and imipenem. There was no susceptibility difference between cefazolin and vancomycin (p = 0.999) and between ceftazidime and imipenem (p = 1.0). Colistin was superior to ceftazidime (p = 0.047) against GNB. The GNB resistant to amikacin (n = 14) were equally susceptible to ceftazidime and colistin; resistant to ceftazidime (n = 16) were susceptible to colistin; and resistant to colistin (n = 7) were susceptible to ceftazidime. The preference of VRSI members (n = 231) practicing in India was a vancomycin-ceftazidime combination (82%), vancomycin for GPC (94%), ceftazidime for GNB (61%), and voriconazole for fungi (74%). CONCLUSION: In EMS, GPC had good susceptibility to vancomycin; GNB had good susceptibility to ceftazidime and colistin. Given the lower resistance of colistin, a vancomycin-colistin combination could be an alternative empiric treatment in post-cataract endophthalmitis in India.

Evaluation of optical coherence tomography biomarkers to differentiate favourable and unfavourable responders to intravitreal anti-vascular endothelial growth factor treatment in retinopathy of prematurity.

OBJECTIVE: Evaluation of optical coherence tomography biomarkers in predicting treatment response to intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) Bevacizumab, in aggressive retinopathy of prematurity (A-ROP). METHODS: Non-contact ultra-widefield (NC-UWF) fundus imaging with integrated UWF guided swept source Optical coherence tomography (SS-OCT) was performed prospectively in preterm babies before and after intravitreal anti-VEGF (Bevacizumab) monotherapy. OCT biomarkers were analysed in eyes that reached complete vascularization versus others. RESULTS: Eyes with retinal vessels reaching near ora serrata were labelled as regressed ROP and vascularised retina (Group1). Eyes with reactivation of ROP needing laser or vitreoretinal surgery or eyes with peripheral avascular retina (PAR) at 16th week post-injection were considered as Group 2. Pre-injection baseline OCT showed a hyperreflectivity of inner retinal layers in 12 out of 46 eyes in Group 1 versus 30 out of 34 eyes in Group 2 (p value 0.002). None of the eyes in Group 1 showed choroidal thinning at posterior pole as compared to 14 out of 34 eyes in Group 2 (p value 0.001). Intraretinal hypo reflective Cystic changes at fovea were seen in 16 out of 46 eyes in Group 1 and 2 out of 34 eyes in Group 2 (p value 0.012). CONCLUSION: Pre-injection swept source OCT biomarkers could predict the treatment outcomes of anti-VEGF (Bevacizumab) monotherapy in A-ROP eyes. Hyperreflectivity of inner retinal layers and choroidal thinning had poorer and unpredictable response to anti-VEGF injection whereas, cystic changes at fovea predicted favourable response.

Evaluating the utility of inflammation score in post-cataract surgery endophthalmitis. Results from a prospective study in India. EMS Report #4.

PURPOSE: To investigate if inflammation score (IS), calculated from the cornea, anterior chamber, iris, and vitreous, indicates endophthalmitis severity. METHODS: In a prospective study, consecutive adults with a clinical diagnosis of post-cataract endophthalmitis within 6 weeks of surgery were recruited. Patients were allocated to IS-based primary treatment (IS < 10: intravitreal injection and IS ≥ 10: vitrectomy) and randomized to two intravitreal antibiotics combinations (vancomycin + ceftazidime and vancomycin + imipenem). Undiluted vitreous microbiology work-up included culture susceptibility, polymerase chain reaction, Sanger sequencing, and targeted next-generation sequencing. RESULTS: The average age of 175 people was 63.4 ± 10.7 years and included 52.6% small incision cataract surgery and 47.4% phacoemulsification surgery. Severe endophthalmitis (IS ≥ 20), diagnosed in 27.4% of people, had a shorter time to symptoms (average 5.4 vs 8.7 days; P = 0.018), poorer presenting vision (all ≤ hand motion), higher culture positivity (50% vs 30.7%; P = 0.032), and higher Gram-negative bacterial infection (70.8% vs 46.2%; P = 0.042). For IS ≥ 20 discriminant and Gram-negative infection, Spearman's coefficient was 0.7 [P < 0.0001, 95% confidence interval (CI) 0.59-0.82], with an area under the receiver operating characteristic curve of 0.9 (95% CI 0.85-0.94, P < 0.0001), a Youden index J of 0.74, a sensitivity of 87.2%, and a specificity of 87.5%. The final vision of >20/400 and >20/100 was regained in 50.2% and 29.1% of people, respectively. The susceptibility of common Gram-positive cocci and Gram-negative bacilli was the highest for vancomycin (95.0%) and colistin (88.6%), respectively. NGS detected polymicrobial infection in 88.5% of culture-negative endophthalmitis. CONCLUSIONS: Higher inflammation scores indicated severe disease and Gram-negative infection in post-cataract endophthalmitis.

Endophthalmitis Management Study-A Prospective Randomized Clinical Trial on Postoperative Endophthalmitis Management in India: An Interim Analysis. Endophthalmitis Management Study Report #3.

PURPOSE: An interim analysis of the Endophthalmitis Management Study to examine the outcome of inflammation score (IS)-based treatment and antibiotic susceptibility. DESIGN: A prospective randomized study. PATIENTS AND METHODS: IS was measured on a 0-4 scale from presenting signs in 4 cardinal ocular tissues. The eyes with IS <10 received vitreous tap and intravitreal antibiotics, whereas eyes with IS ≥10 received vitrectomy and intravitreal antibiotics. These eyes were randomized to 2 intravitreal antibiotic combinations: (1) vancomycin and ceftazidime and (2) vancomycin and imipenem. Microbiology workup of undiluted vitreous included microscopy, culture-susceptibility, Sanger, and targeted next-generation sequencing. The clinical and microbiology outcomes were analyzed for advanced (IS = ≥20) and less advanced (IS = <10) endophthalmitis. RESULTS: Interim analysis was performed after the Endophthalmitis Management Study recruited 56.85% (248/436) of patients and completed 54.6% (238/436) of microbiology workup. A 90-day follow-up was completed in 90.8% (168/185) of eligible people. In eyes with IS ≥20, the time to symptoms was shorter (5.8 ± 6.7 vs 8.5 ± 9.1 d; P = 0.015), and the need for additional treatment was higher (95.8% vs 53.1%; P = 0.0267). Good final vision was associated with good presenting vision (r = 0.30) and IS-based treatment decisions (r = 0.170). Microbiology positivity was 55.9%. Eyes with IS <10 had a higher Gram-positive cocci (33.9% vs 4.8%; P = 0.013) infection. Gram-positive cocci were most susceptible to vancomycin (95.7%), and Gram-negative bacilli to colistin (95.7%). CONCLUSIONS: Considering both IS and presenting vision, rather than only one of them, helps in making appropriate management decisions for acute postoperative endophthalmitis.

Solar retinopathy in India: Clinical presentation and demographic distribution in 253 patients (349 eyes).

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), which was followed by moderate 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.

Combined rhegmatogenous and tractional retinal detachment in a child with incontinentia pigmenti managed by scleral imbrication with scleral buckle.

We report for the first time a child with incontinentia pigmenti presenting with acute-onset rhegmatogenous retinal detachment in association with pre-existing tractional retinal detachment. Due to the combined nature of this detachment, complex vector forces acting on the retina makes this a difficult to treat situation. A single surgery of modified scleral imbrication with scleral buckle was effective in reattaching the retina by providing a very high buckle indent to accommodate all the complex vector forces. Commonly used procedure of vitrectomy and silicone oil usage was avoided as that often requires multiple surgeries and may result in variable and unpredictable response.

Application and validation of a novel inflammatory score in the clinical grading of infectious endophthalmitis: The endophthalmitis management study - Report 2.

Purpose: This study was conducted to describe and validate a novel inflammatory score (IS) system in the management of infectious endophthalmitis. Methods: This was a prospective comparative non-interventional observational study. The study included the patients with clinical signs and symptoms of acute post-cataract surgery endophthalmitis (surgery within 6 weeks) with visual acuity from 6/18 to light perception. IS was scored by the clinical picture at two-levels of four ocular tissues on a scale of 0 (normal) to 4 (severe). Four masked graders of different levels of experience evaluated slit-lamp photographs. The concordance correlation coefficient was assessed between the slit-lamp clinical grading and photographic grading. We measured the concordance correlation coefficient, Pearson's correlation (indicating precision), and the bias correction factor (indicating the accuracy). Results: The study included 43 eyes of 43 patients. The concordance correlation coefficient was 0.99 (95% CI 0.995 to 0.998). Both Pearson's correlation coefficient and the bias correction were 0.99. The interclass correlation coefficient (ICC) was measured. The intra-rater ICC was 0.833 with good agreement (95% CI, 0.711 to 0.906; P < 0.001). Inter-rater ICC for consistency was 0.92 (95% CI 0.87 to 0.95). Inter-rater ICC for absolute agreement was 0.86 (95% CI 0.66 to 0.93). Conclusion: Currently used IS scoring in the study is a reliable, reproducible, and easy-to-apply scale to measure inflammation severity in endophthalmitis. We propose that it can have applications in decision-making for primary treatment and monitoring progression in acute infectious endophthalmitis.

Fovea sparing internal limiting membrane peeling for idiopathic macular holes-Report of unfavourable outcomes of a surgical technique.

PURPOSE: To describe the outcomes of fovea-sparing internal limiting membrane peeling for idiopathic macular holes. METHOD: This was a prospective, interventional case series in patients with idiopathic macular holes. Patients underwent fovea-sparing internal limiting membrane (ILM) peeling with the help of a finesse loop. The primary outcome measure was successful anatomical closure. Secondary outcome measures were postoperative improvement in best corrected visual acuity (BCVA) or any surgical complications. RESULTS: The study included 22 eyes of 22 patients (median age of 61 (IQR 58 to 66) years). The median basal diameter of the holes was 1054 (IQR 961.5 to 1278) microns, while the median minimal linear diameter was 697 (IQR 461.5 to 786) microns. Successful anatomic closure was achieved in nine cases out of 22 (40.9%). BCVA improved from 20/125 preoperatively to 20/80 at the end of the follow-up. There was no difference in baseline parameters between eyes with closure, versus eyes with an open hole. One eye had an iatrogenic break in an attempt to reinitiate peeling and create a fovea-sparing flap. One of the eyes had an ERM formation at end of 3 months. CONCLUSION: Our outcomes of fovea-sparing ILM peeling in idiopathic macular holes were unfavourable. The residual ILM could be causing tangential traction resulting in non-closure.

Non-contact widefield neonatal retinal imaging for retinopathy of prematurity using the Clarus 700 high resolution true colour reflectance imaging.

OBJECTIVE: To illustrate the role of non-contact widefield retinal imaging (NC-WFI) of retinopathy of prematurity (ROP) using the Clarus 700 high resolution true colour reflectance imaging. METHODS: All babies were examined by the vitreoretinal faculty in a tertiary eye care centre from a period of March 2021 to November 2021 using the indirect ophthalmoscope after pupillary dilatation. ROP grading was done according to the revised ICROP (2005) classification. NC-WFI was then performed using the Clarus 700 high resolution true colour reflectance imaging (Carl Zeiss Meditec, Dublin, CA) in the retina diagnostic set up of a tertiary eye care centre. RESULTS: A total of 22 babies (44 eyes) underwent NC-WFI from March 2021 to November 2021. 13 unique cases of retinopathy of prematurity with images captured on Clarus 700 and the clinical summary is described. CONCLUSION: Clarus is a non-contact wide field imaging (NC-WFI) system that can capture high resolution and true colour images (images of the fundus appear similar colour to direct observation by ophthalmoscopy) helping in more accurate diagnosis and grading of the severity of ROP.

Effectiveness and future implications of COVID-19-related risk stratification for managing retinopathy of prematurity: The Indian twin cities retinopathy of prematurity study report number 10.

Purpose: To evaluate the effectiveness and future implications of COVID-related risk stratification for managing retinopathy of prematurity (ROP). Methods: A prospective study was conducted at a tertiary eye care center from the beginning of the lockdown in India from 23 March 2020 till the end of the first phase of lockdown on 29 May 2020. We evaluated 200 prematurely born infants (< 34 weeks of gestational age) using the new safety guideline protocols for low-risk babies developed in conjunction with the Indian ROP Society for care during the COVID-19 pandemic. Low risk included babies born at more than 30 weeks of gestational age, post menstrual age 34 weeks or above at presentation, more than 1000 grams of birth weight, and stable systemically with good weight gain. Results: New guidelines were implemented in 106 (53%) infants who were low risk while 94 (47%) infants with high risk were followed up as per the old guidelines. Out of the 106 infants (212 eyes) managed by the new guidelines, good outcome (group 1) was seen in 102 (96.2%) infants. Twenty-seven of the 102 infants had some form of ROP and 5 of these infants needed treatment. None of the low-risk babies with no detachment at presentation managed by new guidelines required surgery later (group 2). Two (1.9%) infants came with retinal detachment at presentation and underwent successful surgery (group 3) and two infants (1.9%) were lost to follow up. Conclusion: New risk stratification during the COVID-19 pandemic was an efficient and safe strategy in managing low-risk ROP babies.

Jet stream related iatrogenic retinal breaks during vitreo-retinal surgery.

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.

Acute Retinal Necrosis as a presenting ophthalmic manifestation in COVID 19 recovered patients.

Purpose: Infection by the SARS-CoV2 virus results in an immune dysregulated state which can predispose to reactivation of Herpes viruses. This report describes the development of Acute Retinal Necrosis (ARN) in two patients who had recovered from SARS-CoV2 infection.Methods: Observational report of two consecutive patients who presented with ARN after having recovered from SARS-CoV-2 infection.Results: Case 1 was a 5-year-old child with extensive peripheral necrotizing retinitis. Case 2 was a 61-year-old gentlemen with bilateral retinal detachment with sieve-like breaks and optic atrophy. Both patients had recovered from SARS- Cov-2 infection 1 month ago. PCR from vitreous sample of both patients was positive for Herpes simplex virus. Case 1 was treated with oral valacyclovir. Case 2 underwent surgery in both eyes for retinal detachmentConclusion: Immune dysregulation after COVID-19 infection can result in reactivation of herpesvirus and may lead to development of ARN.

Rare case of Terson's syndrome and viral retinitis due to dengue haemorrhagic fever in an infant.

Dengue haemorrhagic fever with consequent thrombocytopaenia can lead to intracranial haemorrhage and Terson's syndrome that can lead to visual problems. Simultaneously, the dengue virus can cause typical viral retinitis like picture in the eye. Early funduscopy and vision assessment is desirable in all dengue patients. In our case, an infant with dengue haemorrhagic fever and intracranial haemorrhage developed not only simultaneous bilateral vitreous and subinternal limiting membrane haemorrhage due to Terson's syndrome from the indirect effect of thrombocytopaenia but also typical chorioretinitis possibly due to the direct effect of the virus on the retina. The vitreoretinal surgical outcome was satisfactory in this case.