Transpupillary-Guided Trans-Scleral Transplantation of Subretinal Grafts in a Retinal Degeneration Mouse Model.

Transplantation of photoreceptor cells and retinal pigment epithelial (RPE) cells provide a potential therapy for retinal degeneration diseases. Subretinal transplantation of therapeutic donor cells into mouse recipients is challenging due to the limited surgical space allowed by the small volume of the mouse eye. We developed a trans-scleral surgical transplantation platform with direct transpupillary vision guidance to facilitate the subretinal delivery of exogenous cells in mouse recipients. The platform was tested using retinal cell suspensions and three-dimensional retinal sheets collected from rod-rich Rho::EGFP mice and cone-rich OPN1LW-EGFP;NRL-/- mice, respectively. Live/dead assay showed low cell mortality for both forms of donor cells. Retinal grafts were successfully delivered into the subretinal space of a mouse model of retinal degeneration, Rd1/NS, with minimum surgical complications as detected by multimodal confocal scanning laser ophthalmoscope (cSLO) imaging. Two months post-transplantation, histological staining demonstrated evidence of advanced maturation of the retinal grafts into 'adult' rods and cones (by robust Rho::EGFP, S-opsin, and OPN1LW:EGFP expression, respectively) in the subretinal space. Here, we provide a surgical platform that can enable highly accurate subretinal delivery with a low rate of complications in mouse recipients. This technique offers precision and relative ease of skill acquisition. Furthermore, the technique could be used not only for studies of subretinal cell transplantation but also for other intraocular therapeutic studies including gene therapies.

Risk of Tertiary, Quaternary, and Quinary Proliferative Vitreoretinopathy: Analysis of a Nationwide Database (2010-2017).

OBJECTIVE: Primary proliferative vitreoretinopathy (PVR) is established as an important cause of the failed repair of a fresh retinal detachment (RD) and the consequent need for secondary repair. However, the burden of multiple repairs beyond the initial failure has not been studied in detail. We aimed to determine the association between primary PVR and the occurrence of tertiary, quaternary, and quinary RD repairs, using a nationwide database. DESIGN: Retrospective cohort study of insurance claims. SUBJECTS: Cases of rhegmatogenous RD that underwent primary surgical repair. METHODS: Cases of primary RD repair from 2010 to 2017 were categorized based on the absence (P0 group) or presence (P1 group) of primary PVR. In each group, we analyzed the frequency of subsequent RD repair procedures with concurrent PVR. MAIN OUTCOME MEASURE: The risk of secondary and higher multiples of PVR-associated RD repair. RESULTS: A total of 27 137 cases were included, with 24 500 (90.3%) in the P0 group and 2637 (9.7%) in the P1 group. The frequency (%) of cases ultimately requiring secondary, tertiary, quaternary, and quinary repair in P0 versus P1 was 1.88 versus 10.24 (P < 0.001), 0.26 versus 2.50 (P < 0.001), 0.07 versus 0.64 (P < 0.001), and 0.03 versus 0.08 (P = 0.272), respectively. The risk of undergoing secondary repair was higher in the P1 than in the P0 group (hazard ratio [HR], 6.02; 95% confidence interval [CI], 5.24-6.92; P < 0.001). The risk of undergoing tertiary repair was also higher in the P1 than in the P0 group (HR, 1.67; CI, 1.23-2.28; P = 0.001). There was no difference in the risk of undergoing quaternary repair between the groups (HR, 0.76; CI, 0.41-1.40; P = 0.37). Senary repairs were not detected in this dataset. CONCLUSIONS: Primary PVR may increase the risk of requiring multiple sequential retinal reattachment surgeries beyond the initial repair failure. Retinal detachment cases with primary PVR at the initial presentation of RD were more likely to undergo secondary and tertiary repairs than cases without primary PVR. Health care claims analysis may be a useful tool to study population-based estimates for multiple recurrences of RD in cases with PVR. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Telemedicine Curriculum in an Ophthalmology Residency Program.

Background The COVID-19 pandemic has accelerated the adoption of telemedicine in the field of ophthalmology. Despite the increasing utilization of telemedicine, there is a lack of formal training in ophthalmology residency programs to ensure ophthalmologists are prepared to conduct virtual eye exams. Objective This article aims to assess the impact of an ophthalmic telemedicine curriculum on ophthalmology residents' self-reported knowledge acquisition in conducting telemedicine eye exams, perceived ability to diagnose, manage, and triage common eye diseases, and evaluate their attitudes toward the current and future use of teleophthalmology. Methods This single-center study at Massachusetts Eye and Ear used a nonvalidated pre- and postcurriculum survey conducted during the 2020 to 2021 academic year among ophthalmology residents. Participants engaged in an ophthalmic telemedicine curriculum that consisted of interactive didactic lectures and electronic postdidactic assessments. Results Twenty-four residents (100%) completed a precurriculum survey, while 23 of 24 (95.8%) residents completed both the telemedicine curriculum and a postcurriculum survey. On a five-point Likert scale, the median interquartile range (IQR) scores for confidence with setup/logistics, history taking, examination, documentation, and education increased from 2.5 (2.0-4.0) to 4.0 (3.5-4.5) ( p = 0.001), 3.0 (3.0-4.0) to 5.0 (4.0-5.0) ( p < 0.001), 2.0 (1.8-2.0) to 4.0 (3.5-4.0) ( p < 0.001), 2.0 (1.0-2.0) to 4.0 (3.0-4.0) ( p < 0.001), and 2.5 (2.0-3.0) to 4.0 (4.0-4.0) ( p < 0.001), respectively. The median (IQR) scores for comfort with ethics/professionalism, disparities and conducting patient triage, diagnosis, and management increased from 2.0 (2.0-2.3) to 4.0 (3.0-4.0) ( p < 0.001), 2.0 (2.0-2.0) to 3.0 (3.0-4.0) ( p < 0.001) and 3.0 (2.0-3.0) to 4.0 (3.0-4.0) ( p = 0.001), 2.0 (2.0-3.0) to 3.0 (3.0-4.0) ( p < 0.001), and 3.0 (2.0-3.0) to 3.0 (3.0-4.0) ( p = 0.008), respectively. Conclusion The implementation of an ophthalmic telemedicine curriculum increased resident confidence and self-reported knowledge across all logistical and clinical components of virtual ophthalmic care. Formal telehealth curricula can address an unmet educational need of resident trainees in an era of rapid uptake and utilization of telehealth services.

A Review of Ophthalmic Telemedicine for Emergency Department Settings.

BACKGROUND: Patients presenting to emergency departments for ophthalmic emergencies benefit from prompt evaluation. However, Few emergency departments (EDs) have ophthalmologists on call, and eye care provided in EDs without ophthalmic services can be inaccurate. METHODS: We review the current state of ophthalmic telemedical care in EDs and highlight important considerations when implementing telemedicine in this setting. RESULTS: Telemedicine allows ophthalmologists to work with on-site emergency care providers to interview and examine patients remotely in EDs, enabling proper assessment of patient history, visual acuity, pupils, intraocular pressure, as well as the anterior and posterior segment. To date, patients' perceptions of this new model of care have been largely positive. DISCUSSION: The use of telemedical consultations for remote evaluation of patients with ophthalmic complaints stands to improve the quality of care provided to patients and extend the reach of remote ophthalmologists. The onset of the COVID-19 pandemic and the risk of in-person care further highlights the potential for telemedicine to augment existing models of emergency care.

Screening first-degree relatives of glaucoma patients reveals barriers to participation.

PURPOSE: To report the results of a glaucoma screening campaign targeting first-degree relatives of glaucoma patients in South India. METHODS: 1598 glaucoma patients were contacted via letter or letter and phone call and asked to bring their siblings and children to a glaucoma screening. Participants underwent standardised eye examinations and completed questionnaires that assessed barriers to participation and awareness of glaucoma risk. Two-proportion z-tests were used to compare categorical data. Costs associated with the screening were recorded. RESULTS: 206 probands (12.9%) attended the screening along with 50 siblings and children. Probands were nearly twice as likely to attend if they had been contacted via both letter and phone call rather than letter only. Over half of probands reported that their relatives could not participate because they did not live in the region, and one-fifth reported that their relatives had other commitments. Fifty-eight per cent of the siblings and children who attended did not know that they were at increased risk for glaucoma due to their family history, and 32.0% did not know that the relative who had invited them to the screening had glaucoma. Thirteen siblings and children (26.0% of those who attended) were found to have findings concerning for glaucoma. The average cost per first-degree relative who was screened was INR2422 (£26). CONCLUSION: Participation in this glaucoma screening campaign was poor. The major barrier to participation was distance from the screening site and associated indirect costs. Better strategies for bringing first-degree relatives in for examinations are needed.

Localized Structural and Functional Deficits in a Nonhuman Primate Model of Outer Retinal Atrophy.

Purpose: Cell-based therapy development for geographic atrophy (GA) in age-related macular degeneration (AMD) is hampered by the paucity of models of localized photoreceptor and retinal pigment epithelium (RPE) degeneration. We aimed to characterize the structural and functional deficits in a laser-induced nonhuman primate model, including an analysis of the choroid. Methods: Macular laser photocoagulation was applied in four macaques. Fundus photography, optical coherence tomography (OCT), dye angiography, and OCT-angiography were conducted over 4.5 months, with histological correlation. Longitudinal changes in spatially resolved macular dysfunction were measured using multifocal electroretinography (MFERG). Results: Lesion features, depending on laser settings, included photoreceptor layer degeneration, inner retinal sparing, skip lesions, RPE elevation, and neovascularization. The intralesional choroid was degenerated. The normalized mean MFERG amplitude within lesions was consistently lower than control regions (0.94 ± 0.35 vs. 1.10 ± 0.27, P = 0.032 at month 1, 0.67 ± 0.22 vs. 0.83 ± 0.15, P = 0.0002 at month 2, and 0.97 ± 0.31 vs. 1.20 ± 0.21, P < 0.0001 at month 3.5). The intertest variation of mean MFERG amplitudes in rings 1 to 5 ranged from 13.0% to 26.0% in normal eyes. Conclusions: Laser application in this model caused localized outer retinal, RPE, and choriocapillaris loss. Localized dysfunction was apparent by MFERG in the first month after lesion induction. Correlative structure-function testing may be useful for research on the functional effects of stem cell-based therapy for GA. MFERG amplitude data should be interpreted in the context of relatively high intertest variability of the rings that correspond to the central macula. Sustained choroidal insufficiency may limit long-term subretinal graft viability in this model.

Association of Patient Characteristics With Delivery of Ophthalmic Telemedicine During the COVID-19 Pandemic.

Importance: Telemedicine has been shown to have had reduced uptake among historically marginalized populations within multiple medical specialties during the COVID-19 pandemic. An evaluation of health disparities among patients receiving ophthalmic telemedical care during the pandemic is needed. Objective: To evaluate disparities in the delivery of ophthalmic telemedicine at Massachusetts Eye and Ear (MEE) during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective, cross-sectional study analyzed clinical visits at a single tertiary eye care center (MEE) from January 1 to December 31, 2020. Patients who had ophthalmology and optometry clinical visits at the MEE during the study period were included. Exposures: Telemedicine vs in-person clinical encounters. Main Outcomes and Measures: Variables associated with use of ophthalmic telemedicine during the study period. Results: A total of 2262 telemedicine ophthalmic encounters for 1911 patients were included in the analysis. The median age of the patients was 61 (interquartile range, 43-72) years, and 1179 (61.70%) were women. With regard to race and ethnicity, 87 patients (4.55%) identified as Asian; 128 (6.70%), as Black or African American; 23 (1.20%), as Hispanic or Latino; and 1455 (76.14%), as White. On multivariate analysis, factors associated with decreased receipt of telemedical care included male sex (odds ratio [OR], 0.86; 95% CI, 0.77-0.96), Black race (OR, 0.69; 95% CI, 0.56-0.86), not speaking English (OR, 0.63; 95% CI, 0.48-0.81), educational level of high school or less (OR, 0.83; 95% CI, 0.71-0.97), and age (OR per year of age, 0.99; 95% CI, 0.989-0.998). When comparing telephone- and video-based telemedicine visits, decreased participation in video-based visits was associated with age (OR per year of age, 0.96; 95% CI, 0.94-0.98), educational level of high school or less (OR, 0.54; 95% CI, 0.29-0.99), being unemployed (OR, 0.28; 95% CI, 0.12-0.68), being retired (OR, 0.22; 95% CI, 0.10-0.42), or having a disability (OR, 0.09; 95% CI, 0.04-0.23). Conclusions and Relevance: The findings of this cross-sectional study, though limited to retrospective data from a single university-based practice, suggest that historically marginalized populations were less likely to receive ophthalmic telemedical care compared with in-person care during the first year of the COVID-19 pandemic in the US. Understanding the causes of these disparities might help those who need access to virtual care.

Lessons Learned From 2 Large Community-based Glaucoma Screening Studies.

Community-based screening programs have had limited success in preventing vision loss from glaucoma due to overall low prevalence of glaucoma, screening limitations, and barriers to follow-up appointments. This editorial highlights lessons learned from 2 large prospective trials: the Philadelphia Telemedicine Glaucoma Detection and Follow-up Study and the Screening To Prevent Glaucoma Study. While some lessons are specific to ophthalmology, many lessons are applicable to screening for asymptomatic diseases in underserved, vulnerable communities.

Investigation of the Accuracy of a Low-Cost, Portable Autorefractor to Provide Well-Tolerated Eyeglass Prescriptions: A Randomized Crossover Trial.

PURPOSE: To compare patient preferences for eyeglasses prescribed using a low-cost, portable wavefront autorefractor versus standard subjective refraction (SR). DESIGN: Randomized, cross-over clinical trial. PARTICIPANTS: Patients aged 18 to 40 years presenting with refractive errors (REs) to a tertiary eye hospital in Southern India. METHODS: Participants underwent SR followed by autorefraction (AR) using the monocular version of the QuickSee device (PlenOptika Inc). An independent optician, masked to the refraction approach, prepared eyeglasses based on each refraction approach. Participants (masked to refraction source) were randomly assigned to use SR- or AR-based eyeglasses first, followed by the other pair, for 1 week each. At the end of each week, participants had their vision checked and were interviewed about their experience with the eyeglasses. MAIN OUTCOME MEASURES: Patients preferring eyeglasses were chosen using AR and SR. RESULTS: The 400 participants enrolled between March 26, 2018, and August 2, 2019, had a mean (standard deviation) age of 28.4 (6.6) years, and 68.8% were women. There was a strong correlation between spherical equivalents using SR and AR (r = 0.97, P < 0.001) with a mean difference of -0.07 diopters (D) (95% limits of agreement [LoA], -0.68 to 0.83). Of the 301 patients (75.2%) who completed both follow-up visits, 50.5% (n = 152) and 49.5% (n = 149) preferred glasses prescribed using SR and AR, respectively (95% CI, 45.7-56.3; P = 0.86). There were no differences in demographic or vision characteristics between participants with different preferences (P > 0.05 for all). CONCLUSIONS: We observed a strong agreement between the prescriptions from SR and AR, and eyeglasses prescribed using SR and AR were equally preferred by patients. Wider use of prescribing based on AR alone in resource-limited settings is supported by these findings.

The Direct Healthcare Cost of Stargardt Disease: A Claims-Based Analysis.

Purpose: Stargardt disease (SD) is the most common juvenile macular degeneration and a leading cause of uncorrectable childhood blindness. The progressive and incurable nature of this chronic condition entails a long-term financial burden on affected individuals. The economic costs of SD have not been characterized in detail, so we aimed to estimate the direct healthcare cost of SD.Methods: Outpatient administrative claims data (2010-2014) for patients with SD were analyzed from the IBM® MarketScan® Commercial Claims and Encounters Database. Two comparison groups were selected: nonexudative age-related macular degeneration (AMD) and bilateral sensorineural hearing loss (SHL). Gross median payments per year of insurance coverage were calculated.Results: A total of 472,428 patients were analyzed (5,015 SD, 369,750 SHL and 97,663 AMD patients respectively). The payment per year of insurance coverage for SD (median: 105.58 USD, IQR: 50.53 USD-218.71 USD) was higher than that of SHL (median: 51.01 USD, IQR: 25.66 USD-121.66 USD, p < .001) and AMD (median: 76.20 USD, IQR: 38.00 USD-164.86 USD, p < .001). When adjusted for age, sex, year of first service, and type of benefit plan, the annual payment for SD was 47.83 USD higher than SHL (p < .001) and 17.34 USD higher than AMD (p < .001).Conclusions: There is a significant direct healthcare cost associated with SD. The annual per-patient cost of SD was higher than SHL, another condition that causes sensory impairment in people of all ages, and nonexudative AMD which causes a similar pattern of visual loss that typically begins later in life. The total lifetime per-patient cost of SD may exceed that of nonexudative AMD.

Risk Factors for Repeat Keratoplasty after Endothelial Keratoplasty in the Medicare Population.

PURPOSE: To evaluate long-term rates of repeated keratoplasty after endothelial keratoplasty (EK), and to explore risk factors associated with graft failure. DESIGN: Retrospective, cohort study. METHODS: Population-based using 2010-2019 Medicare carrier claims. STUDY POPULATION: Medicare beneficiaries aged ≥65 years who underwent endothelial keratoplasty (EK) procedures. Main outcome measures were 1) occurrence of repeated keratoplasty for the overall cohort as well as stratified by clinical indication, and 2), risk factors associated with repeated keratoplasty. The probability of undergoing repeated keratoplasty for different indications was estimated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards regression model was constructed to determine patient and physician factors associated with the risk of repeated keratoplasty. RESULTS: A total of 94,829 Medicare EK procedures (N = 71,040 unique patients) were included in the analysis. Over the study period, 11,013 of 94,829 EK procedures were followed by repeated keratoplasty. The overall probability of receiving a repeated keratoplasty was 6.1% at 6 months, 7.6% at 1 year, 14.3% at 5 years and 16.9% at 8 years. The probability of repeated keratoplasty was highest for procedures performed for prior failed grafts: 10.2% at 1 year, 29.9% at 8 years. Whereas 6.4% and 11.4% of grafts performed for Fuchs' endothelial dystrophy (FED) required repeated keratoplasty at 1 and 8 years of follow-up, respectively. For bullous keratoplasty and/or corneal edema, 8.6% and 22% of grafts underwent repeated keratoplasty at 1 and 8 years, respectively. In a multivariate analysis, patient factors associated with increased risk of repeated keratoplasty were black (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.20-1.38) or Asians (HR: 1.26; 95% CI: 1.10-1.45) having a glaucoma diagnosis (HR: 1.53; 95% CI: 1.46-1.60), prior glaucoma surgery (HR: 1.26; 95% CI: 1.18-1.35), and concurrent glaucoma surgery (HR: 1.31; 95% CI: 1.20-1.44). Surgeons with higher EK volumes had a decreased risk of repeated keratoplasty. Physicians who graduated medical school >30 years previously had increased risk of repeated keratoplasty compared to those who graduated within 10 years (HR: 1.16; 95% CI: 1.10-1.23). CONCLUSIONS: Blacks or Asians, comorbid glaucoma, concurrent or prior glaucoma surgery, and lower volumes of surgery are associated with increased risk of repeated keratoplasty. Racial disparities identified in this study warrant further investigation.

Long-Term Outcomes from an Intraoperative Bleb Needling Procedure Augmented with Continuous Infusion.

PURPOSE: To investigate long-term outcomes of a modified bleb needling technique performed in the operating room in controlling intraocular pressure (IOP) and to report risk factors for procedure failure. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: One hundred six eyes of 98 consecutive patients undergoing intraoperative bleb needling with a continuous infusion of balanced salt solution at the Wilmer Eye Institute, Johns Hopkins Hospital, in the setting of a failed trabeculectomy or express shunt, between May 2011 and December 2015. METHODS: Postoperative data were collected between May 2011 and August 2019. Success was defined as achieving a previously determined target IOP regardless of (qualified success) or without (complete success) glaucoma medications. Patients who underwent additional glaucoma surgery were censored in the survival analysis. MAIN OUTCOME MEASURES: Primary outcome measures included IOP, attainment of target IOP, and number of glaucoma medications used at different time points pre- and post-operatively. RESULTS: Needling was performed in 106 eyes at an average of 4.3 years from the time of trabeculectomy (standard deviation [SD], 6.5 years) and an average baseline IOP of 20.7 mmHg (SD, 7.2 mmHg). Further glaucoma surgery was required for 33 eyes. We observed a 70% qualified success rate with a mean IOP lowering of 25% (95% confidence interval [CI], 13.8%-36.4%) at 1 year after surgery and a 52% qualified success rate and 44.3% reduction in IOP (95% CI, 34.9%-53.6%) at 5 years after surgery. Nearly half and a third of the eyes did not require medications after 1 and 5 years, respectively. The average medication reduction was 0.8 at year 1 (95% CI, 0.5-1.1) and 0.4 at year 5 (95% CI, -0.2 to 1.0). Postoperative complications were uncommon. Poorer outcomes were not associated with the age of the bleb but were more likely in Black patients. CONCLUSIONS: Reductions in IOP were maintained in most patients over the long term using a modified bleb needling technique, despite an average time from trabeculectomy of over 4 years. No significant adverse events were observed. Bleb needling may defer or avoid more invasive procedures such as tube-shunts or repeat trabeculectomy.

Postoperative Complications in Medicare Beneficiaries Following Endothelial Keratoplasty Surgery.

PURPOSE: To determine national-level incidence rates of major postoperative complications following endothelial keratoplasty (EK) procedures and to stratify these rates based on EK indications over an 8-year period using Medicare claims data. DESIGN: Retrospective, cohort study. METHODS: Setting: population-based; study population: Medicare beneficiaries aged ≥65 years who underwent EK procedures; main outcome measurements: 1) occurrence of major postoperative complications (i.e., endophthalmitis, choroidal hemorrhage, infectious keratitis, cystoid macular edema [CME], retinal detachment [RD], or RD surgery) following EK surgery; 2) time-to-event analysis for glaucoma surgery; and 3) occurrence of graft complications. RESULTS: A total of 94,829 EK procedures (n = 71,040 unique patients) were included in the analysis. Of the total, 29% of patients had pre-existing glaucoma. The overall 90-day cumulative incidence of postoperative endophthalmitis and choroidal hemorrhage following EK was 0.03% and 0.05%, respectively. The overall 1-year cumulative rates of RD or RD surgery, infectious keratitis, and CME were 1.0%, 0.8%, and 4.1%, respectively. Approximately 7.6%, 12.2%, and 13.8% of all eyes in this study needed glaucoma surgery at 1-, 5-, and 8-years of follow-up, respectively. The probability of glaucoma surgery among patients with pre-existing glaucoma was 29% vs. 8% among those without pre-existing glaucoma at 8 years. The cumulative probabilities of developing any graft complications were 13%, 23.2%, and 27.1% at 1, 5, and 8 years, respectively, of follow-up. On average, patients undergoing EK procedures for a prior failed graft had the highest rate of complications, whereas those with Fuchs' corneal endothelial dystrophy had the lowest. CONCLUSIONS: The incidence of major postoperative complications including endophthalmitis, retinal detachment, and choroidal hemorrhage following EK procedures is low. A high proportion of eyes undergoing EK eventually require glaucoma surgery and experience graft-related complications. Postoperative outcomes are typically worse for patients undergoing EK for prior failed grafts than for those undergoing EK for Fuchs' corneal endothelial dystrophy.

Anti-vascular endothelial growth factor for neovascular glaucoma.

BACKGROUND: Neovascular glaucoma (NVG) is a potentially blinding, secondary glaucoma. It is caused by the formation of abnormal new blood vessels, which prevent normal drainage of aqueous from the anterior segment of the eye. Anti-vascular endothelial growth factor (anti-VEGF) medications are specific inhibitors of the primary mediators of neovascularization. Studies have reported the effectiveness of anti-VEGF medications for the control of intraocular pressure (IOP) in NVG. OBJECTIVES: To assess the effectiveness of intraocular anti-VEGF medications, alone or with one or more type of conventional therapy, compared with no anti-VEGF medications for the treatment of NVG. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register); MEDLINE; Embase; PubMed; and LILACS to 22 March 2019; metaRegister of Controlled Trials to 13 August 2013; and two additional trial registers to 22 March 2019. We did not use any date or language restrictions in the electronic search for trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of people treated with anti-VEGF medications for NVG. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the search results for trials, extracted data, and assessed risk of bias, and the certainty of the evidence. We resolved discrepancies through discussion. MAIN RESULTS: We included four RCTs (263 participants) and identified one ongoing RCT. Each trial was conducted in a different country: China, Brazil, Egypt, and Japan. We assessed the trials to have an unclear risk of bias for most domains due to insufficient information. Two trials compared intravitreal bevacizumab combined with Ahmed valve implantation and panretinal photocoagulation (PRP) with Ahmed valve implantation and PRP. We did not combine these two trials due to substantial clinical and statistical heterogeneity. One trial randomised participants to receive an injection of either an intravitreal anti-VEGF medication or placebo at the first visit, followed by non-randomised treatment according to clinical findings after one week. The last trial randomised participants to PRP with and without ranibizumab, but details of the study were unavailable for further analysis. Two trials that examined IOP showed inconsistent results. One found inconclusive results for mean IOP between participants who received anti-VEGF medications and those who did not, at one month (mean difference [MD] -1.60 mmHg, 95% confidence interval [CI] -4.98 to 1.78; 40 participants), and at one year (MD 1.40 mmHg, 95% CI -4.04 to 6.84; 30 participants). Sixty-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 60% without anti-VEGF medications. In another trial, those who received anti-VEGF medications were more likely to reduce their IOP than those who did not receive them, at one month (MD -6.50 mmHg, 95% CI -7.93 to -5.07; 40 participants), and at one year (MD -12.00 mmHg, 95% CI -16.79 to -7.21; 40 participants). Ninety-five percent of the participants with anti-VEGF medications achieved IOP ≤ 21 mmHg, versus 50% without anti-VEGF medications. The certainty of a body of evidence was low for this outcome due to limitations in the design and inconsistency of results between studies. Post-operative complications included anterior chamber bleeding (3 eyes) and conjunctival hemorrhage (2 participants) in the anti-VEGF medications group, and retinal detachment and phthisis bulbi (1 participant each) in the control group. The certainty of evidence is low due to imprecision of results and indirectness of evidence. No trial reported the proportion of participants with improvement in visual acuity, proportion of participants with complete regression of new iris vessels, or the proportion of participants with relief of pain and resolution of redness at four- to six-week, or one-year follow-up. AUTHORS' CONCLUSIONS: Currently available evidence is uncertain regarding the long-term effectiveness of anti-VEGF medications, such as intravitreal ranibizumab or bevacizumab or aflibercept, as an adjunct to conventional treatment in lowering IOP in NVG. More research is needed to investigate the long-term effect of these medications compared with, or in addition to, conventional surgical or medical treatment in lowering IOP in NVG.

Tonometers-which one should I use?

Although several factors are known to play a role in the development and progression of glaucoma, intraocular pressure (IOP) remains the only modifiable risk factor. Medical and surgical treatments for glaucoma both aim to reduce IOP to minimize disease progression. Tonometry is therefore an essential element of the ophthalmological exam. There are several types of tonometers available currently. These range from well-established instruments that have been in clinical use for decades to new devices, which are the result of recent technological advances. The various instruments have advantages and disadvantages that affect their suitability for a given setting, purpose, and patient population. In this review, we aim to describe the most commonly available tonometers today along with their advantages, disadvantages, and applicability.

Pancreatic Fistula and Delayed Gastric Emptying After Pancreatectomy: Where do We Stand?

Pancreatic resection has become a feasible treatment of pancreatic neoplasms, and with improvements in surgical techniques and perioperative management, mortality associated with pancreatic surgery has decreased considerably. Despite this improvement, a high rate of complications is still associated with these procedures. Among these complications, delayed gastric emptying (DGE) and postoperative pancreatic fistula (POPF) have a substantial impact on patient outcomes and burden our healthcare system. Technical modifications and postoperative approaches have been proposed to reduce rates of both POPF and DGE in patients undergoing pancreatectomy; however, to date, their rates have remained unchanged. In the present study, we summarize the findings of the most significant studies that have investigated these complications. In particular, several studies focused on technical modifications including extent of dissection, stent placement, nature of anastomosis, type of reconstruction, and application of biological or non-biological agents to site of anastomosis. Moreover, postoperatively, drain placement, duration of drain usage, postoperative feeding, and use of pharmacological agents were studied to reduce rates of POPF and DGE. In this review, we summarize the most relevant literature on this fundamental aspect of pancreatic surgery. Despite studies identifying the potential benefit of technical modifications and postoperative approaches, these findings remain controversial and suggest need for further extensive investigation. Most importantly, we recommend that all surgeons performing these procedures base their practice on the most updated and highest available level of evidence.

Patients' visual experience during phacoemulsification cataract surgery and associated fear.

BACKGROUND: Data from several published studies indicate that patients undergoing phacoemulsification cataract surgery can experience a variety of visual sensations which can result in fear. This phenomenon has not been studied in Pakistan to-date. We examined the visual experience and its associated fear among patients undergoing phacoemulsification cataract surgery under topical anaesthesia. METHODS: This cross-sectional study was carried out in Aga Khan University Hospital, a tertiary care hospital, in Karachi, Pakistan from August 2010 to July 2011. Adults >18 years of age scheduled to undergo cataract surgery (phacoemulsification with intraocular lens implantation) under topical anaesthesia by a single surgeon were included. A structured questionnaire was used to collect data on socio-demographics, intraoperative visual experiences and subsequent reaction to these sensations. Participants were asked if they experienced visual sensations such as colours, shapes and movements during surgery. Moreover, they were asked if they developed fear due to these sensations. RESULTS: Fifty three patients (mean age: 60.4 ± 12.4 years) were enrolled. Thirty (56.6%) of them were men and 23 (43.4%) were women. All of them reported having experienced visual sensations during surgery, the most common being light perception (100%), different colours (77.4%), movements of instruments or surgeon's hands (37.7%) and different shapes (7.5%) such as circles, clouds and patches. The most common colours perceived included white (46.2%), blue (35.8%), red (30.2%) and yellow (30.2%). One out of every four (26.4%) participants reported having developed fear due to these visual sensations. Only 4 (7.5%) reported having received preoperative counselling regarding such sensations. CONCLUSION: Patients in our study experienced a variety of visual sensations during cataract surgery under topical anaesthesia. The prevalence of frightening visual sensations is higher than that reported in all previous published studies on the subject and needs to be addressed through targeted interventions.

Safety and efficacy of fluocinolone acetonide intravitreal implant (0.59 mg) in birdshot retinochoroidopathy.

PURPOSE: To report the treatment outcomes of the fluocinolone acetonide intravitreal implant (0.59 mg) in patients with birdshot retinochoroidopathy whose disease is refractory or intolerant to conventional immunomodulatory therapy. METHODS: A retrospective case series involving 11 birdshot retinochoroidopathy patients (11 eyes). Eleven patients (11 eyes) underwent surgery for fluocinolone acetonide implant (0.59 mg). Treatment outcomes of interest were noted at baseline, before fluocinolone acetonide implant, and then at 6 months, 1 year, 2 years, 3 years, and beyond 3 years. Disease activity markers, including signs of ocular inflammation, evidence of retinal vasculitis, Swedish interactive threshold algorithm-short wavelength automated perimetry Humphrey visual field analysis, electroretinographic parameters, and optical coherence tomography were recorded. Data on occurrence of cataract and raised intraocular pressure were collected in all eyes. RESULTS: Intraocular inflammation was present in 54.5, 9.9, 11.1, and 0% of patients at baseline, 6 months, 1 year, 2 years, 3 years, and beyond 3 years after receiving the implant, respectively. Active vasculitis was noted in 36.3% patients at baseline and 0% at 3 years of follow-up. More than 20% (47.61-67.2%) reduction in central retinal thickness was noted in all patients with cystoid macular edema at 6 months, 1 year, 2 years, and 3 years postimplant. At baseline, 54.5% patients were on immunomodulatory agents. This percentage decreased to 45.45, 44.4, and 14.28% at 1 year, 2 years, and 3 years postimplant, respectively. Adverse events included increased intraocular pressure (54.5%) and cataract formation (100%). CONCLUSION: The data suggest that fluocinolone acetonide implant (0.59 mg) helps to control inflammation in otherwise treatment-refractory cases of birdshot retinochoroidopathy. It is associated with significant side effects of cataract and ocular hypertension requiring treatment.

Combination approaches to potentiate immune response after photodynamic therapy for cancer.

Photodynamic therapy (PDT) has been used as a cancer therapy for forty years but has not advanced to a mainstream cancer treatment. Although it has been shown to be an efficient way to destroy local tumors by a combination of non-toxic dyes and harmless visible light, it is its additional effects in mediating the stimulation of the host immune system that gives PDT great potential to become more widely used. Although the stimulation of tumor-specific cytotoxic T-cells that can destroy distant tumor deposits after PDT has been reported in some animal models, it remains the exception rather than the rule. This realization has prompted several investigators to test various combination approaches that could potentiate the immune recognition of tumor antigens that have been released after PDT. This review will cover these combination approaches using immunostimulants including various microbial preparations that activate Toll-like receptors and other receptors for pathogen-associated molecular patterns, cytokines growth factors, and approaches that target regulatory T-cells. We believe that by understanding the methods employed by tumors to evade immune response and neutralizing them, more precise ways of potentiating PDT-induced immunity can be devised.