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.

Aflibercept vs. dexamethasone implant for recalcitrant diabetic macular edema in pseudophakic eyes - 1-year outcomes from a quazi-randomized study in India.

PURPOSE: To assess the safety and efficacy of intravitreal Aflibercept (IVA) versus dexamethasone (DEX) implant for treating recalcitrant diabetic macular edema (DME) in pseudophakic eyes at 1-year follow-up. DESIGN: Retrospective comparative case series. PARTICIPANTS: Data of all patients diagnosed with DME between January 2019 and December 2021, who underwent 4-monthly doses of intravitreal ranibizumab but had persistent DME [central macular thickness (CMT) within 10% of baseline value] were extracted from a computerized database. Of these, only pseudophakic eyes that underwent either IVA or DEX implant and had at least 1-year follow-up were included for analysis. METHODS: DEX implant was preferred before December 2020 and IVA after this time point. In the IVA group, patients were followed up every month while DEX were followed at least every 3 months. Reinjections were considered when vision dropped by at least 1 Snellen's line or CMT increased by at least 10% from the previous visit in both groups. MAIN OUTCOME MEASURES: Comparison of change in vision and CMT at 1-year follow-up in DEX versus IVA groups. RESULTS: Eighty-four eyes of 84 patients aged 54.4 + 4.4 years were included, 39 (46%) received DEX and 45 (54%) received IVA. Groups were comparable for baseline vision and CMT. Vision improved equally in both groups from 0.83 + 0.15 logMAR to 0.52 + 0.10 logMAR at 3 months ( P < 0.01) and then stabilized till 1 year. However, eyes in the IVA group were 6.5 times more likely (Odds ratio = 6.45, 95% CI = 1.3 - 31.9) to achieve >3-line improvement in vision. The CMT reduction was also comparable between groups (-169 + 51 in DEX vs. -174 + 49 in IVA, P = 0.67). More eyes in the IVA group required >3 injections (91% vs. 69% in DEX, P = 0.01). The IOP was significantly higher at 6 and 9 months in the DEX group and 5 eyes (13%) required IOP lowering medications. CONCLUSION: In pseudophakic eyes with recalcitrant DME not responding to ranibizumab, switching to IVA or DEX implant results in equal visual improvement and CMT reduction. Though >3-line improvement occurs more frequently with IVA, this comes at the expense of a greater number of injections and follow-up visits.

Incidence, clinical features, risk factors, and outcomes of Intraocular inflammation following Brolucizumab in Indian eyes - A multicentric study.

Purpose: To report the incidence, clinical features, potential risk factors, and outcomes of intraocular inflammation (IOI) following brolucizumab in Indian eyes. Methods: All consecutive patients diagnosed with brolucizumab-induced IOI from 10 centers in eastern India between October 2020 and April 2022 were included. Results: Of 758 injections given during the study period across centers, 13 IOI events (1.7%) were recorded attributable to brolucizumab. The IOI occurred after the first dose in two eyes (15%) (median 45 days after brolucizumab), second dose in six eyes (46%) (median = 8.5 days), and third dose (39%) in the remaining five eyes (median 7 days). Reinjections of brolucizumab were administered at a median interval of 6 weeks (interquartile range = 4-10 weeks) in the 11 eyes, where IOI occurred after the second or third dose. Eyes that experienced IOI after the third dose had received a significantly greater number of previous antivascular endothelial growth factor injections (median = 8) compared to those who developed it after the first or second dose (median = 4) (P = 0.001). Anterior chamber cells were seen in almost all eyes (n = 11, 85%), while peripheral retinal hemorrhages were seen in two eyes, and one eye showed branch artery occlusion. Two-thirds of patients (n = 8, 62%) recovered with a combination of topical and oral steroids, while remaining recovered with topical steroids alone. Irreversible visual loss was not seen in any eye, and median vision recovered to pre-IOI levels by 3 months' time point. Conclusion: Brolucizumab-induced IOI was relatively rare, occurring in 1.7% of eyes, was more common after the second or third injection, especially in those who required frequent reinjections every 6 weeks, and occurred earlier with increasing number of previous brolucizumab injections. Continued surveillance is necessary even after repeated doses of brolucizumab.

Vitrectomized vs non-vitrectomized eyes in DEX implant treatment for DMO-Is there any difference? the VITDEX study.

OBJECTIVE: We aimed to compare visual and anatomical outcome in vitrectomized and non-vitrectomized eyes treated with dexamethasone (DEX) implant due to diabetic macular oedema (DMO). DESIGN: Multicenter, retrospective, interventional study. PARTICIPANTS: 236 eyes from 234 patients with DMO with or without previous vitrectomy performed with follow-up of 12 months. METHODS: Records were reviewed for cases of DMO treated with DEX implant in vitrectomized and not vitrectomized eyes. Best corrected visual acuity (BCVA), central subfoveal thickness (CST), and intraocular pressure (IOP) were recorded at baseline and 12 months after treatment with DEX implants. Correlations between vitreous status and visual and anatomical outcome, as well as safety profile were analysed. MAIN OUTCOME MEASURES: BCVA and CST over follow-up period. SECONDARY OUTCOMES: cataract rate formation, intraocular pressure increase, number of implants needed. RESULTS: The non-vitrectomized group included 130 eyes (55.1%), the vitrectomized group included 106 eyes (44.9%). The groups were well balanced for age and gender (p = 0.540, and p = 0.053, respectively). Both groups showed statistically significant improvement in BCVA and CST (for all groups: p < 0.001). There was no significant difference between the groups in terms of change in vision (p = 0.89) and anatomy (p = 0.65). The mean number of DEX implants given during follow-up was 3.5 in both groups, and there was no significant difference between the groups (p = 0.81). CONCLUSION: We demonstrated similar anatomical and functional efficacy of DEX implant in non-vitrectomized and vitrectomized eyes. Its efficacy was not influenced by full vitrectomy for diabetic retinopathy complications. Safety profile was well balanced between groups.

Preferred practice patterns in aphakia management in adults in India: A survey.

Purpose: To assess different approaches in the management of aphakia in adults in Indian ophthalmologists via an online survey. Methods: A survey-monkey based online questionnaire was fielded to Indian ophthalmologists in accordance with the CHERRIES guidelines. We recorded participants' demographics, practice settings, and preferred surgical options including the type of intraocular lens (IOL) preferred when encountering a case of aphakia in adults with and without adequate capsular support. Differences between anterior segment (AS) surgeons and vitreoretinal (VR) surgeons as well as differences between surgeons with more or less than 10 years of surgical experience were evaluated using analytic statistics. Results: Of the 481 surgeons who responded to the survey, 369 (77%) were AS surgeons and the remaining 112 (23%) were VR surgeons and represented all regions of India. When encountering posterior capsular rent during cataract surgery, a three-piece IOL in the ciliary sulcus was the most preferred (n = 275, 57%) when there was adequate capsular support, while a retrofixated iris-claw IOL (n = 91, 19%) was the commonest choice in eyes without adequate capsular support. With associated nucleus drop, 85% of surgeons preferred to refer the patient to a VR surgeon and left the eye aphakic. Multivariable logistic regression showed that VR surgeons were more than six times likely to prefer a scleral fixated intraocular lens (SFIOLs) [odds ratio (OR) = 6.5, 95% confidence interval (CI) = 3.4-12.5, P < 0.001] and surgeons with >10 years of experience were also twice more likely to prefer an SFIOL (OR = 2.4, 95% CI = 1.2-4.9, P = 0.02). Conclusion: The choice of IOL in absence of capsular support in adult eyes differs between AS and VR surgeons and is also influenced by the surgeon's experience.

Initial experience in treating polypoidal choroidal vasculopathy with brolucizumab in Indian eyes - A multicenter retrospective study.

Purpose: To report the initial experience of managing treatment-resistant and treatment-naïve eyes with polypoidal choroidal vasculopathy (PCV) by using brolucizumab 6 mg. Methods: This was a retrospective multicentric series of all consecutive eyes with PCV treated with brolucizumab. Treatment resistance was defined as taking at least six prior anti-VEGF injections over the past 1 year and showing persistent disease activity in the form of intra (IRF) or subretinal fluid (SRF) or both. All patients were treated on a pro re nata (PRN) basis and followed up monthly. Retreatment was considered when either SRF or IRF were present at any time point during the study. Results: We included 21 eyes of 21 patients with PCV with a mean age of 65.1 ± 9.9 years, of which 16 eyes (76%) were treatment-resistant. The mean follow-up period from receiving the first brolucizumab was 27.3 ± 3.3 weeks. Of the 21 eyes, seven eyes (33%) received three injections during follow-up, 13 eyes (62%) received two injections, and one eye received one injection. The mean injection-free interval was 12 ± 1.2 weeks. The median pretreatment vision was 0.6 logMAR (IQR = 0.47-1 logMAR) and improved to 0.3 logMAR (IQR = 0.25-0.6 logMAR), whereas the mean macular thickness improved from 443 ± 60 µm at baseline to 289 ± 25 µm (P < 0.001) at the last follow-up period. None of the eyes experienced any intraocular inflammation across 48 injection sessions. Conclusion: Brolucizumab is safe and effective in controlling PCV disease in both treatment-resistant and treatment-naïve eyes.

Examining socio-spatial mobility patterns among colon cancer patients after diagnosis.

Given the growing number of cancer survivors, it is important to better understand socio-spatial mobility patterns of cancer patients after diagnosis that could have public health implications regarding post-diagnostic access to care for treatment and follow-up surveillance. In this exploratory study, residential histories from LexisNexis were linked to New Jersey colon cancer cases diagnosed from 2006 to 2011 to examine differences in socio-spatial mobility patterns after diagnosis by stage at cancer diagnosis, sex, and race/ethnicity. For the colon cancer cases, we summarized and compared the number of residences and changes in the residential census tract and neighborhood poverty after the diagnosis. We found only minor changes in neighborhood poverty among the cases during the follow-up period after diagnosis. During the follow-up period of up to 10 years after diagnosis, 67% of the patients did not move to a different residential census tract, and 10.8% moved from New Jersey to another state. Cases that moved to a different census tract changed after diagnosis were generally less wealthy than non-movers, but the destination of relocation varied by race/ethnicity and socioeconomic status. We also found a significant association between residential mobility and stage at diagnosis, whereby patients diagnosed with colon cancer at an early stage were more likely to be movers. This study contributes to understanding of the socio-spatial mobility patterns in colon cancer patients and may help to inform cancer research by summarizing the extent to which colon cancer patients move after diagnosis.

Outcomes of preoperative bevacizumab in diabetics with nonclearing vitreous hemorrhage without tractional detachment - A quasi-randomized retrospective study.

PURPOSE: To assess whether preoperative bevacizumab (BVZ) in treatment-naïve eyes with proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH) without tractional retinal detachment (TRD) leads to lesser macular edema and better visual outcome compared to eyes that do not receive BVZ. METHODS: This quasi-randomized retrospective study included 217 treatment-naïve eyes with nonclearing VH without TRD that had vitrectomy with or without BVZ and had a minimum 6-months follow-up. Postoperative variables, including visual acuity (BCVA), central macular thickness (CMT) at 1 month, and need for additional anti-VEGF injections till 6 months follow-up, were recorded for analysis. RESULTS: Of the 217 eyes, 107 eyes (49%) received preoperative BVZ and 110 (51%) did not. Groups were comparable in terms of preoperative characteristics. At 1 month, mean CMT was significantly higher in eyes without BVZ (310 ± 33 m vs. 246 ± 34m; P < 0.001). The likelihood of developing center-involving DME at 1 month after vitrectomy was 67% lower if the eye received preoperative BVZ (OR = 0.33, 95%CI = 0.18-2.54, P = 0.56). Though BCVA improved significantly in both groups at 1 month, it was 1/3rd of a line better in the BVZ group (b coefficient = -0.035 logMAR, 95%CI = -0.04 to -0.008 logMAR, P = 0.01). CONCLUSION: Preoperative BVZ in treatment-naïve eyes with PDR and VH but without TRD lead to better macular status and marginally improved vision at 1 month, which was maintained at 6 months. In view of these results, patients may be offered BVZ only when it is readily affordable to them.

A Delphi method based consensus statement for surgical management of proliferative diabetic retinopathy in India.

PURPOSE: To derive consensus statements for surgical management of proliferative diabetic retinopathy (PDR) for vitreoretinal (VR) surgeons. METHODS: Thirteen prolific VR surgeons representing all regions of India were invited to participate in a 42-point questionnaire based on the Delphi methodology describing various surgical scenarios commonly encountered in PDR. Consensus was derived using predefined robust analytics. Scenarios that returned a moderate consensus in round 1 were taken to round 2 as per the Delphi methodology. After considering all inputs, the final consensus criteria were developed. RESULTS: A strong consensus was derived about waiting for 4 weeks before considering vitrectomy. In treatment-naïve eyes with fresh vitreous hemorrhage (VH), the wait time was slightly shorter for extramacular tractional retinal detachment (2-4 weeks) and longer (4-6 weeks) for eyes treated previously with laser or anti-VEGF agents. The expert panel recommended using preoperative anti-VEGF only in eyes with large membranes requiring extensive dissection. For post vitrectomy VH, while a conservative approach was recommended for the first episode of VH, experts recommended immediate vitreous lavage for recurrent episodes of VH. In eyes with iris neovascularization, the panel recommended immediate anti-VEGF injection followed by early vitreous lavage in nonresponsive eyes. A strong consensus was derived for stopping antiplatelet agents before surgery, while there was only a moderate consensus for performing vitrectomy for recalcitrant macular edema unresponsive to anti-VEGF injections in the absence of traction. CONCLUSION: This study provides valuable consensus on managing the different scenarios encountered during surgical management of PDR and should help guide the VR surgeons in clinical decision-making.

Geographic clustering of cutaneous T-cell lymphoma in New Jersey: an exploratory analysis using residential histories.

PURPOSE: Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma. Previous studies have reported geographic clustering of CTCL based on the residence at the time of diagnosis. We explore geographic clustering of CTCL using both the residence at the time of diagnosis and past residences using data from the New Jersey State Cancer Registry. METHODS: CTCL cases (n = 1,163) diagnosed between 2006-2014 were matched to colon cancer controls (n = 17,049) on sex, age, race/ethnicity, and birth year. Jacquez's Q-Statistic was used to identify temporal clustering of cases compared to controls. Geographic clustering was assessed using the Bernoulli-based scan-statistic to compare cases to controls, and the Poisson-based scan-statisic to compare the observed number of cases to the number expected based on the general population. Significant clusters (p < 0.05) were mapped, and standard incidence ratios (SIR) reported. We adjusted for diagnosis year, sex, and age. RESULTS: The Q-statistic identified significant temporal clustering of cases based on past residences in the study area from 1992 to 2002. A cluster was detected in 1992 in Bergen County in northern New Jersey based on the Bernoulli (1992 SIR 1.84) and Poisson (1992 SIR 1.86) scan-statistics. Using the Poisson scan-statistic with the diagnosis location, we found evidence of an elevated risk in this same area, but the results were not statistically significant. CONCLUSION: There is evidence of geographic clustering of CTCL cases in New Jersey based on past residences. Additional studies are necessary to understand the possible reasons for the excess of CTCL cases living in this specific area some 8-14 years prior to diagnosis.

Measuring Neighborhood Landscapes: Associations between a Neighborhood's Landscape Characteristics and Colon Cancer Survival.

Landscape characteristics have been shown to influence health outcomes, but few studies have examined their relationship with cancer survival. We used data from the National Land Cover Database to examine associations between regional-stage colon cancer survival and 27 different landscape metrics. The study population included all adult New Jersey residents diagnosed between 2006 and 2011. Cases were followed until 31 December 2016 (N = 3949). Patient data were derived from the New Jersey State Cancer Registry and were linked to LexisNexis to obtain residential histories. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI95) for the different landscape metrics. An increasing proportion of high-intensity developed lands with 80-100% impervious surfaces per cell/pixel was significantly associated with the risk of colon cancer death (HR = 1.006; CI95 = 1.002-1.01) after controlling for neighborhood poverty and other individual-level factors. In contrast, an increase in the aggregation and connectivity of vegetation-dominated low-intensity developed lands with 20-<40% impervious surfaces per cell/pixel was significantly associated with the decrease in risk of death from colon cancer (HR = 0.996; CI95 = 0.992-0.999). Reducing impervious surfaces in residential areas may increase the aesthetic value and provide conditions more advantageous to a healthy lifestyle, such as walking. Further research is needed to understand how these landscape characteristics impact survival.

Residential Mobility and Geospatial Disparities in Colon Cancer Survival.

BACKGROUND: Identifying geospatial cancer survival disparities is critical to focus interventions and prioritize efforts with limited resources. Incorporating residential mobility into spatial models may result in different geographic patterns of survival compared with the standard approach using a single location based on the patient's residence at the time of diagnosis. METHODS: Data on 3,949 regional-stage colon cancer cases diagnosed from 2006 to 2011 and followed until December 31, 2016, were obtained from the New Jersey State Cancer Registry. Geographic disparity based on the spatial variance and effect sizes from a Bayesian spatial model using residence at diagnosis was compared with a time-varying spatial model using residential histories [adjusted for sex, gender, substage, race/ethnicity, and census tract (CT) poverty]. Geographic estimates of risk of colon cancer death were mapped. RESULTS: Most patients (65%) remained at the same residence, 22% changed CT, and 12% moved out of state. The time-varying model produced a wider range of adjusted risk of colon cancer death (0.85-1.20 vs. 0.94-1.11) and resulted in greater geographic disparity statewide after adjustment (25.5% vs. 14.2%) compared with the model with only the residence at diagnosis. CONCLUSIONS: Including residential mobility may allow for more precise estimates of spatial risk of death. Results based on the traditional approach using only residence at diagnosis were not substantially different for regional stage colon cancer in New Jersey. IMPACT: Including residential histories opens up new avenues of inquiry to better understand the complex relationships between people and places, and the effect of residential mobility on cancer outcomes.See related commentary by Williams, p. 2107.

Socioeconomic Disparities in Colon Cancer Survival: Revisiting Neighborhood Poverty Using Residential Histories.

BACKGROUND: Residential histories linked to cancer registry data provide new opportunities to examine cancer outcomes by neighborhood socioeconomic status (SES). We examined differences in regional stage colon cancer survival estimates comparing models using a single neighborhood SES at diagnosis to models using neighborhood SES from residential histories. METHODS: We linked regional stage colon cancers from the New Jersey State Cancer Registry diagnosed from 2006 to 2011 to LexisNexis administrative data to obtain residential histories. We defined neighborhood SES as census tract poverty based on location at diagnosis and across the follow-up period through 31 December 2016 based on residential histories (average, time-weighted average, time-varying). Using Cox proportional hazards regression, we estimated associations between colon cancer and census tract poverty measurements (continuous and categorical), adjusted for age, sex, race/ethnicity, regional substage, and mover status. RESULTS: Sixty-five percent of the sample was nonmovers (one census tract); 35% (movers) changed tract at least once. Cases from tracts with >20% poverty changed residential tracts more often (42%) than cases from tracts with <5% poverty (32%). Hazard ratios (HRs) were generally similar in strength and direction across census tract poverty measurements. In time-varying models, cases in the highest poverty category (>20%) had a 30% higher risk of regional stage colon cancer death than cases in the lowest category (<5%) (95% confidence interval [CI] = 1.04, 1.63). CONCLUSION: Residential changes after regional stage colon cancer diagnosis may be associated with a higher risk of colon cancer death among cases in high-poverty areas. This has important implications for postdiagnostic access to care for treatment and follow-up surveillance. See video abstract: http://links.lww.com/EDE/B705.

A multi-fold string kernel for sequence classification.

A novel framework is proposed to classify biological sequences using a kernel. It considers the topological information along with the primary structural information. The widely used string kernel for sequence classification does not take into account the structural information which might be available for biological sequences. The proposed kernels incorporate the additional structural information and thus make the features more informative.

Structural prediction of dynamic Bayesian network with partial prior information.

The prediction of the structure of a hidden dynamic Bayesian network (DBN) from a noisy dataset is an important and challenging task. This work presents a generalized framework to infer the DBN network structure with partial prior information. In the proposed framework, the partial information about the network structure is provided in the form of prior. The proposed method makes use of the prior information regarding the presence and as well as absence of some of the edges. Using the noisy dataset and partial prior information, this method is able to infer nearly accurate structure of the network. The proposed method is validated using simulated datasets. In addition, two real biological datasets are used to infer hidden biological interaction networks.

Aspergillus-induced malignant glaucoma.

PURPOSE: To report a case of Aspergillus flavus-induced keratomycotic malignant glaucoma. METHODS: A 48-year-old woman presented with a severe corneal ulcer. She had received topical steroids for 10 days before presentation. RESULTS: Microbiological studies revealed A. flavus as the offending pathogen. Nonresponsive high intraocular pressure with associated shallow anterior chamber was present. With a diagnosis of keratomycotic malignant glaucoma, the patient underwent therapeutic keratoplasty with cataract extraction with posterior chamber wash. However, there was a recurrence of malignant glaucoma in the postoperative period. Patient underwent limited pars plana vitrectomy. CONCLUSIONS: Keratomycotic malignant glaucoma is a rare complication of severe fungal ulcer. We believe that the use of topical steroids in this case probably led to increased fungal penetration, with the formation of a lens-iris fungal mass and subsequent malignant glaucoma. Nonresponse to medical therapy warrants urgent surgical intervention. To the best of our knowledge, Aspergillus-induced keratomycotic glaucoma has never been reported previously. This report also highlights that therapeutic keratoplasty with cataract extraction alone may not be sufficient for management of such cases, and a limited pars plana vitrectomy may be needed.