Brolucizumab-associated intraocular inflammation in Indian patients by VRSI study group.

CONTEXT: Concerns about brolucizumab's (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020. PURPOSE: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India. SETTINGS AND DESIGN: Retrospective multicentric, survey-based study. METHODS: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis. RESULTS: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1-65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better. CONCLUSIONS: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.

Toxic anterior segment syndrome (TASS): A review and update.

Toxic anterior segment syndrome (TASS) is an acute, sterile, postoperative inflammatory reaction of the anterior segment without vitreous involvement, following an uncomplicated and uneventful ocular surgery, having broad and multiple etiologies. The symptoms of decreased visual acuity and ocular discomfort generally occur within the first 12-48 h after intraocular surgery. The clinical signs include prominent limbus-to-limbus corneal edema, anterior chamber cells, aqueous flare, fibrinous inflammation, and/or keratic precipitates. There can be sight-threatening complications of TASS, such as permanent corneal decompensation, intractable glaucoma, and cystoid macular edema. The causes of TASS are emerging and being reported, so are the newer treatment options for managing the inflammation and its complications. Prevention guidelines for TASS are being updated, and a traceability system for surgical instruments and intraocular fluids used during the surgery is being perpetually developed. It is important to recognize TASS and start treatment on an immediate effect. Hereby, we review the literature on TASS, emphasizing its etiology, pathophysiology, management, prognosis, complications, and the importance of prevention as well as prompt recognition.

Use of 30 gauge needle to prevent hypotony during silicone oil removal.

Silicone oil (SO) is used as an intraocular tamponade after complex vitreoretinal surgeries because of its properties such as transparency, inertness, high surface tension, and interfacial tension with water. The only disadvantage of SO tamponade is the need for a second surgery for its removal. However, there is a risk of ocular hypotony soon after the removal of the infusion cannula, especially in retinal vascular conditions, such as diabetic retinopathy. We hereby present a silicone oil removal (SOR) technique using a 30 G needle that prevents intraocular hypotony during SOR.

Efficacy of a single injection of brolucizumab in neovascular age-related macular degeneration on visual acuity and micromorphometry.

Purpose: To assess short-term efficacy of a single injection of brolucizumab in neovascular AMD. Methods: This was a multicenter, retrospective chart review of 25 eyes of 25 patients who received a single injection of brolucizumab. Visual acuity (VA) and optical coherence tomography (OCT) features such as central subfield thickness (CSFT), subretinal fluid (SRF), intraretinal fluid, and pigment epithelial detachment (PED) were recorded at baseline, first month, and third month. Results: Of the 25 eyes, 14 eyes were treatment-naïve and 11 eyes had received previous injections. VA improved from 0.68 ± 0.59 log MAR at baseline to 0.31 ± 0.43 log MAR at the end of 3 months. SRF height in first and third month was significantly reduced from baseline (P < 0.001). Subretinal hyperreflective material height significantly reduced from baseline (P value 0.008 at first month and 0.01 at third month, respectively). CSFT was 464.16 ± 247.97 microns at baseline and showed a significant reduction in first month (P < 0.001) and third month (P < 0.001). There was a significant reduction of PED height from baseline at both follow-ups. None of the eyes showed a recurrence of fluid at the end of 3 months. Conclusion: Our study demonstrated sustained improvement in VA and OCT parameters after a single injection of brolucizumab at 3 months. A longer follow-up may demonstrate even farther effects of a single injection.

Antibiotic prophylaxis for cataract surgery - Practice patterns amongst Indian Ophthalmologists.

Purpose: To assess the current trends in use of perioperative antibiotic prophylaxis, especially intracameral antibiotics (ICAB), for cataract surgery in India. Methods: This was an E-survey using a previously validated questionnaire carried out by the All India Ophthalmological Society (AIOS) in August 2022. An E-mail invitation to complete an online 40-point survey was sent to all members of the AIOS using a digital E-mail service (Survey Monkey) and social media platforms. Results: Out of 1804 total respondents, 58% (n = 1022) reported using routine ICAB prophylaxis. Of those using ICAB, 89% (n = 909) reported using it for all cases, whereas the rest used it for specific indications such as post-PC rent (n = 43), one eyed patient (n = 19), and high-risk cases (n = 50). Commercially available moxifloxacin was by far the commonest agent used for ICAB (n = 686, 67%). Eighty respondents (8%) reported noticing occasional toxic reactions and nontoxic corneal edema (n = 64, 6%) with ICAB. Surgeons with >10 years' experience especially practicing in medical colleges used fewer ICAB (OR = 0.52, 95%CI = 0.38 - 0.72, P < 0,001) compared to younger surgeons (<5-year experience) in solo clinics. The commonest reason for nonadoption of IC antibiotics was "unconvinced of the need to use it in my setting" (n = 296, 52% of those who answered this question). Conclusion: IC antibiotic prophylaxis for cataract surgery has significantly increased in India from 40% in 2017 to 58% in 2022. Commercially available moxifloxacin was preferred by the majority users. Intraocular inflammation may occur occasionally and needs safer formulations to avoid this.

All India Ophthalmological Society (AIOS) Task Force guidelines to prevent intraocular infections and cluster outbreaks after cataract surgery.

Infectious endophthalmitis is a serious and vision-threatening complication of commonly performed intraocular surgeries such as cataract surgery. The occurrence of endophthalmitis can result in severe damage to the uveal and other ocular tissues even among patients undergoing an uncomplicated surgical procedure. If the infections result from common factors such as surgical supplies, operative or operation theater-related risks, there can be a cluster outbreak of toxic anterior segment syndrome (TASS) or infectious endophthalmitis, leading to several patients having an undesirable outcome. Since prevention of intraocular infections is of paramount importance to ophthalmic surgeons, the All India Ophthalmological Society (AIOS) has taken the lead in the formation of a National Task Force to help ophthalmic surgeons apply certain universal precautions in their clinical practice. The Task Force has prepared a handy checklist and evidence-based guidelines to minimize the risk of infectious endophthalmitis following cataract surgery.

Diabetic macular edema treatment guidelines in India: All India Ophthalmological Society Diabetic Retinopathy Task Force and Vitreoretinal Society of India consensus statement.

Diabetic macular edema (DME) is a common cause of moderate visual impairment among people with diabetes. Due to the rising number of people with diabetes in India, the absolute numbers of people with DME are significant. There are several treatment options for DME, and the choice of treatment is based on the availability of retinal specialists and infrastructure for the delivery of treatment. A major challenge is the out-of-pocket expenditure incurred by patients as most treatment options are costly. Treatment also varies based on the associated ocular and systemic conditions. The All India Ophthalmology Society (AIOS) and the Vitreo-Retinal Society of India (VRSI) have developed this consensus statement of the AIOS DR task force and VRSI on practice points of DME management in India. The objective is to describe the preferred practice patterns for the management of DME considering the different presentations of DME in different clinical scenarios.

Microincision phacoemulsification combined with sutureless transpupillary passive silicone oil removal.

PURPOSE: To evaluate the outcomes of combined microincision phacoemulsification with sutureless transpupillary silicone oil (SO) removal using an irrigation probe of bimanual irrigation/aspiration. METHODS: We conducted a single-center retrospective study, including patients who had undergone phacoemulsification with transpupillary removal of SO, which had been used for intraocular tamponade after a previous pars plana vitrectomy. Outcome measures were corrected distance visual acuity (CDVA), refractive error, intraocular pressure (IOP), and endothelial cell count (ECC) evaluated preoperatively and postoperatively at 3-month follow-up. Any intraoperative or postoperative complications, duration of surgery, and final retinal status at 3 months were also noted. RESULTS: Seventy-four eyes (74 patients) were analyzed. The mean interval between SO placement and cataract surgery was 4.73 months (standard deviation [SD]: 1.02). CDVA improved in 66 (89.2%) eyes and remained the same in 8 (10.8%) eyes (P < 0.001). The mean postoperative spherical equivalent was -0.96D (SD: 0.75) at 3 months (P < 0.001). There was a significant drop in IOP from 15.08 mmHg (SD: 2.67) preoperatively to 11.64 mmHg (SD: 2.02) postoperatively (P < 0.001). The average ECC loss was only 5.7% at 3 months postoperatively. The mean surgical duration was 17.20 min (SD: 7.02). One patient had retinal redetachment and required resurgery. At 3 months, the retina was attached in all patients. CONCLUSION: Combined microincision phacoemulsification with transpupillary passive SO removal using irrigation probe of bimanual irrigation/aspiration is a safe, effective, and less invasive technique that offers the main advantage of reduced surgical trauma, and should be reserved for patients with a stable retina, not requiring additional surgical intervention.

Ophthalmology residency trainers' perspective on standardization of residency training in India.

Purpose: The aim of this study was to study the perception of residency trainers about an optimum residency program. Methods: A survey, using a pre-validated questionnaire, was conducted by the Academic and Research Committee of the All India Ophthalmological Society, in 2019-20 with questions directed to teachers in medical colleges and national board of examination's ophthalmology residency programs on demography, teaching experience, imparting clinical and surgical skills, ideal academic schedule and dissertation in the post-graduate residency program. Results: The response rate in the survey was 47.6%. Valid responses were obtained from 309 residency trainers. Of these, 132 of 309 (42.7%) were females. The mean age was 45.3 ± 9.5 years, range 26-68 years. The trainers believed that on a scale of 0-10, clinical skills teaching should be taught, mean ± SD: slit lamp 9.8 ± 0.7; indirect ophthalmoscopy 9.3 ± 1.3; gonioscopy 9.2 ± 1.5; perimetry 8.9 ± 1.5; OCT 8.4 ± 1.9; applanation tonometry 9.5 ± 1.2 and orthoptic evaluation 8.1 (±1.9). A resident should ideally perform independently surgeries (median, inter-quartile range IQR): SICS 50 (IQR 40-100); phaco 50 (20-60); pterygium excision 20 (10-40); DCR 10 (5-20); chalazion 20 (10-50), trabeculectomy 7 (5-15); strabismus 5 (2-10), LASIK and retinal detachment 0. Ideally there should be four lectures, four seminars, four case presentations, five journal clubs and four wet labs every month. Conclusion: Teachers expected their wards to become competent professionals. There was near unanimity about the content of clinical skills training, non-medical skills and academics, but there was a significant variation on extent of surgical training that should be imparted to the residents.

Clinical efficacy and safety of Razumab® (CESAR) study: Our experience with the world's first biosimilar Ranibizumab.

Purpose: : The aim of this study was to evaluate the efficacy and safety of Razumab (the biosimilar Ranibizumab by Intas Pharmaceuticals Ltd.) for the treatment of chorioretinal vascular diseases such as diabetic macular edema (DME), choroidal neovascular membrane (CNVM), and macular edema secondary to retinal vein occlusion (RVO). Methods: : We conducted a single-center, retrospective study, including patients with DME, CNVM, and RVO, who had received treatment with Razumab® between October 2018 and September 2019. Primary outcome measures were the changes in corrected distance visual acuity (CDVA) and central foveal thickness (CFT) from baseline to 1 month and 3 months. Secondary outcome measures included intraocular pressure (IOP) at day 1, any signs of ocular inflammation or systemic adverse events during the follow-up. Results: : One hundred and fifty-three eyes of 141 patients were analyzed. The indications included DME in 70 (45.8%) eyes, CNVM in 70 (45.8%) eyes, and RVO in 13 (8.4%) eyes. Mean CDVA improved from baseline (0.62 ± 0.44) to month 1 (0.45 ± 0.42) and maintained till 3 months (0.42 ± 0.44; P < 0.001). Mean CFT showed significant reduction from baseline (405.68 ± 192.422 µm) to month 1 (286.08 ± 118.36 µm) and month 3 (271 ± 104.24 µm; P < 0.001). None of the eyes recorded IOP >20 mmHg on day 1. No evidence of ocular toxicity or systemic adverse event was noted. Conclusion: : Razumab® showed a rapid improvement in CDVA and CFT in most of the eyes with efficacy observed as early as 1 month and maintained till 3 months. The biosimilar Ranibizumab can be a safe and effective low-cost drug for treating macular diseases.

Essentials of setting up a wet lab for ophthalmic surgical training in COVID-19 pandemic.

Wet labs are an extremely important training tool, especially in times of a global COVID-19 pandemic, where surgical training can be minimal. They help the trainee learn and practice in a risk-free environment, without an imminent of a complication or failure, also allowing them the chance to execute the steps of a surgery repeatedly. We summarize all the key ingredients required from setting up a wet lab to improve the surgical skill of the trainees. The review also discusses various eyeball fixating devices, preparation of the eye for various types of ocular surgeries, and the role of simulation-based training in today's scenario.

A national curriculum for ophthalmology residency training.

We present a residency curriculum for Ophthalmology in India. The document derives from a workshop by the All India Ophthalmological Society (AlOS) which adapted the International Council of Ophthalmology residency curriculum and refined and customized it based on inputs by the residency program directors who participated in the work shop. The curriculum describes the course content, lays down the minimum requirements of infrastructure and mandates diagnostic and therapeutic procedures required for optimal training. It emphasises professionalism, management, research methodology, community ophthalmology as integral to the curriculum. The proposed national ophthalmology residency curriculum for India incorporates the required knowledge and skills for effective and safe practice of ophthalmology and takes into account the specific needs of the country.

Residency Evaluation and Adherence Design Study III: Ophthalmology residency training in India: Then and now-Improving with time?

Purpose: To gauge the differences in ophthalmology residency training, academic, clinical and surgical, in the last three decades of the 20th century and the first decade of the 21st century. Methods: A survey was conducted by the Academic and Research Committee of the All India Ophthalmological Society, in 2014-2016, using a prevalidated questionnaire, which was circulated to ophthalmologists to gauge the practicality of the teaching protocols of clinical and surgical skills during postgraduate residency program. Results: Of the 1005 respondents, 320 ophthalmologists who completed residency between 1967 and 2002 (20th century trained) and 531 who completed a residency in 2003-2012 (21st century trained) fulfilled the inclusion criteria. The average age was 49.2 years (standard deviation [SD] 4) and 32.6 years (SD 4), respectively. Twenty-first century trained ophthalmologists rated their training significantly better than the 20th century trained ophthalmologists for slit lamp examination (P = 0.001), indirect ophthalmoscopy, gonioscopy, automated perimetry, optical coherence tomography, and fundus photography (all having P < 0.001), while the 20th century trained rated their teaching of refraction, synoptophore, diplopia charting better (all P < 0.001). The range of grading was 0-10 in all categories. The median number of surgeries performed independently by 20th century and 21st century trained (during their training period) were: intracapsular cataract extraction (ICCE) 10, 0; extracapsular cataract extraction (ECCE) 43, 18; small incision cataract surgery (SICS) 5, 55; phacoemulsification (Phaco) 0, 1; pterygium excision 20, 15; dacryocystectomy 11, 4; dacryocystorhinostomy 11, 2; chalazion 35, 30; trabeculectomies 5, 0; strabismus correction 0, 0; vitrectomy 0, 0; keratoplasty 0, 0; eyelid surgery 6, 2; and ocular emergencies 18, 20. Conclusion: Teaching of many clinical skills had improved over decades. Cataract surgery training has shifted from ICCE and ECCE to SICS and Phaco, but other surgeries were still taught sparingly. There was an enormous variation across the country in residency training which needs immediate attention.

Prevention and management of postoperative endophthalmitis: A case-based approach.

Endophthalmitis following intraocular surgery is a disastrous complication and can lead to poor visual outcomes and loss of globe integrity. It should be differentiated from toxic anterior segment syndrome (TASS) where management differs drastically. This article presents basic knowledge about postoperative endophthalmitis and describes nine different real-world scenarios ranging from TASS to milder forms of endophthalmitis responding to intravitreal antibiotics alone and more complicated forms associated with corneal involvement, fungal endophthalmitis and cases requiring intraocular lens removal, radical vitrectomy with hyaloid peeling, base dissection, and silicone oil. A case-based approach is followed where practical considerations have been adopted with each case such that it facilitates the readers' ability to apply theoretical knowledge to real-life clinical situations.

Evidence-based review of diabetic macular edema management: Consensus statement on Indian treatment guidelines.

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.

One day wonder: fast resolution of macular edema following intravitreal ranibizumab in retinal venous occlusions.

Macular edema is a significant cause of vision loss in patients with central retinal vein occlusions and branch retinal vein occlusions. Vascular endothelial growth factor (VEGF) appears to be a key factor in the pathogenesis of this disease. Anti-VEGF therapy, such as intravitreal ranibizumab provides an effective treatment against vision-threatening macular edema. We report three patients of retinal vein occlusion with macular edema who demonstrated overnight resolution of macular edema following treatment with intravitreal ranibizumab (0.5 mg). 3D optical coherence tomography (Optovue) was used as a tool for comparison of the macular thickness before and after treatment. The significant reductions in the central foveal thickness demonstrated in these patients one night after intravitreal injections could have significant influence on modifying current treatment protocols. Early treatment of macular edema related to retinal venous occlusive disease with anti-VEGF injections could result in faster visual rehabilitation in these patients.

Biomarkers of the Hedgehog/Smoothened pathway in healthy volunteers.

The Hedgehog (Hh) pathway is involved in oncogenic transformation and tumor maintenance. The primary objective of this study was to select surrogate tissue to measure messenger ribonucleic acid (mRNA) levels of Hh pathway genes for measurement of pharmacodynamic effect. Expression of Hh pathway specific genes was measured by quantitative real time polymerase chain reaction (qRT-PCR) and global gene expression using Affymetrix U133 microarrays. Correlations were made between the expression of specific genes determined by qRT-PCR and normalized microarray data. Gene ontology analysis using microarray data for a broader set of Hh pathway genes was performed to identify additional Hh pathway-related markers in the surrogate tissue. RNA extracted from blood, hair follicle, and skin obtained from healthy subjects was analyzed by qRT-PCR for 31 genes, whereas 8 samples were analyzed for a 7-gene subset. Twelve sample sets, each with ≤500 ng total RNA derived from hair, skin, and blood, were analyzed using Affymetrix U133 microarrays. Transcripts for several Hh pathway genes were undetectable in blood using qRT-PCR. Skin was the most desirable matrix, followed by hair follicle. Whether processed by robust multiarray average or microarray suite 5 (MAS5), expression patterns of individual samples showed co-clustered signals; both normalization methods were equally effective for unsupervised analysis. The MAS5- normalized probe sets appeared better suited for supervised analysis. This work provides the basis for selection of a surrogate tissue and an expression analysis-based approach to evaluate pathway-related genes as markers of pharmacodynamic effect with novel inhibitors of the Hh pathway.

AffyMAPSDetector: a software tool to characterize Affymetrix GeneChip expression arrays with respect to SNPs.

BACKGROUND: Affymetrix gene expression arrays incorporate paired perfect match (PM) and mismatch (MM) probes to distinguish true signals from those arising from cross-hybridization events. A MM signal often shows greater intensity than a PM signal; we propose that one underlying cause is the presence of allelic variants arising from single nucleotide polymorphisms (SNPs). To annotate and characterize SNP contributions to anomalous probe binding behavior we have developed a software tool called AffyMAPSDetector. RESULTS: AffyMAPSDetector can be used to describe any Affymetrix expression GeneChip with respect to SNPs. When AffyMAPSDetector was run on GeneChip HG-U95Av2 against dbSNP-build-123, we found 7286 probes (belonging to 2,582 probesets) containing SNPs, out of which 325 probes contained at least one SNP at position 13. Against dbSNP-build-126, 8758 probes (belonging to 3,002 probesets) contained SNPs, of which 409 probes contained at least one SNP at position 13. Therefore, depending on the expressed allele, the MM probe can sometimes be the transcript complement. This information was used to characterize probe measurements reported in a published, well-replicated lung adenocarcinoma study. The total intensity distributions showed that the SNP-containing probes had a larger negative mean intensity difference (PM-MM) and greater range of the difference than did probes without SNPs. In the sample replicates, SNP-containing probes with reproducible intensity ratios were identified, allowing selection of SNP probesets that yielded unique sample signatures. At the gene expression level, use of the (MM-PM) value for SNP-containing probes resulted in different Presence/Absence calls for some genes. Such a change in status of the genes has the clear potential for influencing downstream clustering and classification results. CONCLUSION: Output from this tool characterizes SNP-containing probes on GeneChip microarrays, thus improving our understanding of factors contributing to expression measurements. The pattern of SNP binding examined so far indicates distinct behavior of the SNP-containing probes and has the potential to help us identify new SNPs. Knowing which probes contain SNPs provides flexibility in determining whether to include or exclude them from gene-expression intensity calculations; selected sets of SNP-containing probes produce sample-unique signatures. AffyMAPSDetector information is available at http://www.binf.gmu.edu/weller/BMC_bioinformatics/AffyMapsDetector/index.html.