Patient satisfaction following a switch from treat-and-extend to observe-and-plan regimen in age-related macular degeneration

ObjectiveStandard treatment of neovascular age-related macular degeneration (nAMD) is intravitreal injections (IVI) of antivascular endothelial growth factor (anti-VEGF) according to treat-and-extend (TnE). Observe-and-plan (OnP), a new regimen based on each individual’s relapse interval lead to fewer clinical visits and has so far shown to be safe in treatment-naïve patients. In this study, we explore patient satisfaction and safety in nAMD when switching from TnE to OnP.Methods and analysis38 participants treated acording to TnE for ≥12 months were included and switched from TnE to OnP with their last stable interval. Main outcome was patient satisfaction (Leeds Satisfaction Questionnaire). Secondary outcomes were best-corrected visual acuity (BCVA), central retinal thickness (CRT) before and 12 months after switch and number of monitoring visits and injections of anti-VEGF 12 months prior to and following switch.ResultsMean patient satisfaction was higher (3.7±0.5 SD) at 12 months after switch from TnE to OnP than before (3.6±0.5 SD, p=0.009, response rate 76%). BCVA and CRT were unchanged. Number of monitoring visits and injections were lower in the 12 months following than prior to switch (p<0.001).ConclusionA switch from TnE to OnP in a non-treatment-naïve population resulted in higher patient satisfaction, while maintaining stable BCVA. This indicates that OnP may be applicable in the large group of nAMD patients that have received IVI for several years. OnP may alleviate the treatment burden on both individual and society of frequent clinical visits while increasing patient satisfaction.

Incidence, progression and risk factors of age-related macular degeneration in 35–95-year-old individuals from three jointly designed German cohort studies

ObjectiveTo estimate age-related macular degeneration (AMD) incidence/progression across a wide age range.Methods and analysisAMD at baseline and follow-up (colour fundus imaging, Three Continent AMD Consortium Severity Scale, 3CACSS, clinical classification, CC) was assessed for 1513 individuals aged 35–95 years at baseline from three jointly designed population-based cohorts in Germany: Kooperative Gesundheitsforschung in der Region Augsburg (KORA-Fit, KORA-FF4) and Altersbezogene Untersuchungen zur Gesundheit der Universität Regensburg (AugUR) with 18-year, 14-year or 3-year follow-up, respectively. Baseline assessment included lifestyle, metabolic and genetic markers. We derived cumulative estimates, rates and risk factor association for: (1) incident early AMD, (2) incident late AMD among no AMD at baseline (definition 1), (3) incident late AMD among no/early AMD at baseline (definition 2), (4) progression from early to late AMD.ResultsIncidence/progression increased by age, except progression in 70+-year old. We observed 35–55-year-old with 3CACSS-based early AMD who progressed to late AMD. Predominant risk factor for incident late AMD definition 2 was early AMD followed by genetics and smoking. When separating incident late AMD definition 1 from progression (instead of combined as incident late AMD definition 2), estimates help judge an individual’s risk based on age and (3CACSS) early AMD status: for example, for a 65-year old, 3-year late AMD risk with no or early AMD is 0.5% or 7%, 3-year early AMD risk is 3%; for an 85-year old, these numbers are 0.5%, 21%, 12%, respectively. For CC-based ‘early/intermediate’ AMD, incidence was higher, but progression was lower.ConclusionWe provide a practical guide for AMD risk for ophthalmology practice and healthcare management and document a late AMD risk for individuals aged <55 years.

Trabeculectomy versus Xen gel implant for the treatment of open-angle glaucoma: a 3-year retrospective analysis

ObjectiveTo compare the two surgical techniques in terms of efficacy, safety, and postoperative management over 36 months of follow-up.MethodsThis retrospective clinical cohort study compared the outcome of trabeculectomy surgery and Xen gel implant in patients having uncontrolled glaucoma. Patients were recruited using the following inclusion criteria: uncontrolled intraocular pressure (IOP) on maximally tolerated medical therapy, healthy conjunctiva freely mobile in the superior sector, open-angle, glaucomatous visual field damage, full follow upfollow-up of at least 36 months. Thirty-four patients were submitted to trabeculectomy and 34 to Xen gel implant. We set the lower limit at 6mmHg mm Hg and the upper limit ≤12 mm Hg for criteria A, upper limit to ≤15 mm Hg for criteria B and upper limit ≤18 mm Hg for criteria C. Criteria for success have been characterizedcharacterised according to whether or not this has been achieved without (complete success) or with IOP -lowering medications (qualified success).ResultsFor all survival curves, trabeculectomy was superior to Xen gel implant. When considering complete success, the log-rank test for criteria A was statistically significant (pp=0.006), marginally significant for criteria B (pp=0.065) and not significant for criteria C (pp=0.23). When qualified success was considered, trabeculectomy was superior to Xen gel for criteria A, B, and C (pp=0.012, pp=0.033 and pp=0.025, respectively). Higher number of post-operative flat chamber and bleb leakage was observed in the trabeculectomy group.ConclusionXen gel implant techniques offer a better safety profile but a lower IOP reduction compared to compared with the gold -standard technique.

Persistent reduction of retinal microvascular vessel density in patients with moderate and severe COVID-19 disease

ObjectiveThis study aims to analyse the possible recovery or worsening in retinal microvasculature after 8 months in a previously studied COVID-19 cohort.Methods and analysisA cross-sectional case–control study and a prospective longitudinal cohort study. Participants were the subjects of our previous study who re-enrolled for a new examination including a fundus photograph (retinography), an optical coherence tomography (OCT) scan and an OCT angiography. COVID-19 diagnosed patients were divided into three groups: group 1: mild disease, asymptomatic/paucisymptomatic subjects who received outpatient care; group 2: moderate disease and group 3: severe disease, both of which required hospital admission because of pneumonia. Statistical analyses were performed using SPSS software (V.23.0). Cross-sectional intergroup differences were analysed by means of analysis of variance for normally distributed variables and the Kruskal-Wallis test for non-normally distributed ones. In reference to the prospective part of the study (intragroup differences, baseline with 8-month comparison), a paired t-test was used for normally distributed data and Wilcoxon signed ranks sum for non-normally distributed data.ResultsThe fovea-centered superficial and deep vascular densities were significantly diminished in severe cases compared with mild cases (p=0.004; p=0.003, respectively, for superficial and deep) and to controls (p=0.014; p=0.010), also in moderate cases to mild group (p=0.004; p=0.003) and to controls (p=0.012; p=0.024). In the longitudinal study, no significant statistical differences were found between baseline and 8-month follow-up vessel density values.ConclusionWe demonstrated persistent reduction in the central vascular area over time in patients with moderate and severe COVID-19.

Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review

ObjectiveTo demonstrate the spectrum of autoimmune retinopathy (AIR) associated with immunotherapy for advanced cutaneous melanoma.Methods and analysisRetrospective chart review on patients with advanced cutaneous melanoma who developed AIR after initiating immunotherapy. Complete ophthalmic examination and relevant ancillary testing were performed on each patient. The presence of AIR-associated anti-retinal antibodies was confirmed by western blot and/or immunohistochemical staining. Ophthalmic and systemic outcomes after treatment for AIR were followed over time. A systematic review of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma was carried out in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsCase 1 developed photopsia and nyctalopia with electroretinographic findings characteristic for melanoma-associated retinopathy 1 week after initiating ipilimumab/nivolumab immunotherapy. Case 2 experienced new severe bilateral visual field loss associated with anti-retinal and anti-optic nerve antibodies while on maintenance nivolumab immunotherapy. Case 3 developed decreased visual acuity due to acute exudative polymorphous vitelliform maculopathy within 2 weeks of initiating ipilimumab/nivolumab immunotherapy. All patients had concurrent extraocular immune-related adverse events in addition to the presence of anti-retinal antibodies on serological testing. 14 published cases of AIR associated with immunotherapy for cutaneous or non-ocular mucosal melanoma were identified and reviewed.ConclusionsImmune checkpoint inhibition can trigger the development of AIR with varied clinical manifestations in patients with advanced cutaneous melanoma. This study highlights the need for close monitoring in cutaneous melanoma patients receiving immunotherapy who develop new visual symptoms with or without funduscopic changes, as well as the potential role for screening of patients prior to initiating immunotherapy.

Medicine treatment of glaucoma in Australia 2012–2019: prevalence, incidence and persistence

ObjectiveMedical therapy can halt or significantly slow the progression of glaucoma if medicines are used in accordance with the guidelines. We used dispensing claims for a 10% sample of all Australians dispensed publicly subsidised glaucoma medicines to determine the prevalence and incidence of glaucoma medicine treatment and to examine treatment persistence between July 2012 and June 2019.MethodsWe estimated incidence and prevalence per 10 000 population for Australian financial years (1 July to 30 June). We defined prevalence as at least one dispensing of any glaucoma medicine and incidence as a dispensing of any glaucoma medicine with no previous dispensing during the preceding 12 months. We estimated duration of treatment for a cohort initiating glaucoma medicines and used Kaplan-Meier methods to estimate the proportion of people persisting on treatment at 6, 12, 18 and 36 months after initiation. We stratified analyses by the number of repeats prescribed at initiation, age, sex and medicine class.ResultsPrevalence remained stable over the study period at around 180/10 000 people/year; incidence was also stable around 36/10 000/year. Among 34 900 people initiating glaucoma medicines, 37.0% remained on treatment at 6 months from initiation, 29.8% at 12 months and 19.2% at 36 months. Median duration of treatment was 13.2 months (IQR: 2.5—not reached) for people initiating prostaglandin analogues and less than 3 months for those initiating other medicine classes.ConclusionPrevalence and incidence of glaucoma treatment have not changed in Australia over the past decade. Persistence to treatment increased with age but remained poor throughout the study period.

Killing efficacy of a new hypothermic corneal storage medium against the micro-organisms frequently found in human donor cornea intended for transplantation

ObjectiveTo study the in vitro killing efficacy of Kerasave (AL.CHI.MI.A Srl), a medium provided with amphotericin B tablet for hypothermic storage of human donor corneas, against relevant contaminants associated with postkeratoplasty infections.Methods and AnalysisThe antimicrobial activity of Kerasave was determined after 0, 3 and 14 days of incubation at 2°C–8°C, inoculating Kerasave and the control medium with 105–106 colony forming units (CFU) of Candida albicans (CA), Fusarium solani (FS), Aspergillus brasiliensis (AB), Staphylococcus aureus (SA), Enterococcus faecalis (EF), Bacillus subtilis spizizenii (BS), Pseudomonas aeruginosa (PA), Enterobacter cloacae (EC) and Klebsiella pneumoniae (KP). Log10 reductions at different time intervals were determined by assessing the number of viable CFU using the serial dilution plating technique.ResultsAfter 3 days, Kerasave induced the highest log10 decrease in the concentrations of KP, PA, CA and EC (5.37, 4.15, 2.97 and 2.67, respectively; all p<0.001). The log10 decreases of SA and EF were 2.27 and 2.11, respectively (all p<0.001). The lowest log10 decrease was observed in BS, AB and FS concentrations (0.25, 0.30 and 0.67, respectively; p<0.001 for BS and AB and p=0.004 for FS). After 14 days, the microbial count of CA, FS, SA, EF, PA and EC further decreased (p=0.006 for FS; p<0.001 for the others).ConclusionKerasave effectively reduced or kept unchanged the microbial concentration of almost all tested strains after 3 days. Thus, this novel medium represents a valuable tool to control the microbial contamination of human donor corneas during hypothermic storage for up to 14 days before transplantation.

Correlation of features on OCT with visual acuity and Gass lesion type in best vitelliform macular dystrophy

ObjectiveTo correlate structural features seen on optical coherence tomography (OCT) with best-corrected visual acuity (BCVA) and Gass lesion type in patients with best vitelliform macular dystrophy (BVMD).Methods and analysisThis is a retrospective case series of consecutive patients with molecularly confirmed BEST1-associated BVMD. OCT scans were reviewed for lesion status and presence of subretinal pillar, focal choroidal excavation (FCE), intraretinal fluid or atrophy. Available OCT angiography images were used to evaluate for the presence of choroidal neovascularisation (CNV). These features were then correlated with BCVA and Gass lesion type.Results95 eyes from 48 patients (mean age 38.9 years, range 4–87) were included. The presence of a pillar (24.2%), FCE (20.0%) and atrophy (7.4%) were associated with poor BCVA (p<0.05). Gass lesion type 1 eyes were correlated with good BCVA (LogMAR <0.4) whereas type 5 eyes had poor BCVA (LogMAR >0.4). Among 65 eyes with longitudinal data (mean follow-up 5.1 years), 7 eyes (10.8%) reverted from higher to lower Gass lesion type; of these, 4 eyes (57.1%) had CNV responsive to intravitreal anti-vascular endothelial growth factor treatment.ConclusionOCT-based structural features are readily identifiable in patients with BVMD and have prognostic importance due to their correlation with BCVA.

Impact of benzalkonium chloride-preserved and preservative-free latanoprost eye drops on cultured human conjunctival goblet cells upon acute exposure and differences in physicochemical properties of the eye drops

ObjectiveTo investigate the short-term impact on human conjunctival goblet cell (GC) survival and mucin release of acute exposure to benzalkonium chloride (BAK) preserved and preservative-free (PF) 0.005% (w/v) latanoprost (LT) eye drops, and to compare the eye drops’ physicochemical properties.Methods and analysisPrimary GC cultures were established from human conjunctival donor tissue. The impact of eye drops on GC survival was assessed using a lactate dehydrogenase assay. Mucin release was evaluated through mucin-specific immunostaining. pH value, osmolality, drop mass and surface tension for all LT eye drops were measured.ResultsAfter application with PF-LT for 30 min (min), the GC survival was maintained compared with control (p=0.9941), while all BAK-LT eye drops reduced survival with approximately 30% (p<0.02). Following application with PF-LT for 30 min, mucin was found around the GC nucleus, as seen in the vehicle control, indicating no secretion. In contrast, BAK-LT caused diffuse staining of mucin, similar to the secretagogue histamine, indicating stimulation of secretion. The pH value of the BAK-LT and PF-LT eye drops were 6.0–6.9 and 6.8, respectively. The osmolality was 258–288 mOsm/kg for the BAK-LT eye drops and 276 for PF-LT eye drops. The mean drop mass was 26–31 mg for the BAK-LT eye drops and 30 mg for PF-LT. The surface tension was lower for all BAK-LT eye drops (31.1–32.1 mN/m) compared with PF-LT (42 mN/m).ConclusionPF-LT compared with various branded and generic LT preparations containing BAK are less cytotoxic when applied to cultured GCs.

Proton beam radiation for iris melanoma: case series and review of literature

ObjectivePurpose of this study is to analyse the visual outcomes, the complication and eye retention rate as well as tumour control data of patients treated with proton beam radiation therapy (PBRT) for iris melanoma.MethodsRetrospective case series and review based on patients’ records. All tumours were categorised according to the American Joint Committee of Cancer staging criteria for primary iris melanoma und underwent either sectorial or whole anterior segment PBRT.ResultsThirteen cases were identified of which five received PBRT of the whole anterior segment and eight received sectorial PBRT. Local tumour control after a mean follow-up of 25 months was 92%. Complications after PBRT included cataract (46%), secondary glaucoma (31%), superficial keratitis (15%) and madarosis (8%). Complications were more common in patients necessitating irradiation of the entire anterior segment than in patients which received sectorial irradiation. Eye retention was achieved in all cases. No statistically significant difference in the mean best corrected visual acuity (BCVA) and intraocular pressure (IOP) was found before and after treatment. Comparison of mean BCVA and IOP between different treatment groups (complete anterior segment vs sectorial irradiation) at the last follow-up visit were also not significantly different. No patient developed metastatic disease during follow-up.ConclusionPBRT is a safe and vision preserving therapeutic modality for iris melanoma. Complete irradiation of the anterior segment is associated with higher complication rates.