A case of secondary multiple evanescent white dot syndrome in a patient with preexisting wet age-related macular degeneration.

Purpose: To report a case of secondary Multiple Evanescent White Dot Syndrome in a patient with preexisting wet age-related macular degeneration. Observation: A 75-year-old male on treat and extend regimen for wet age-related macular degeneration (AMD) presented with a sudden loss of vision and saw central dark shadow in the right eye (RE) for a duration of 1 week. There was no significant history preceding the visual loss. Examination showed a visual acuity (VA) of counting fingers at 1 meter in the right eye and 20/25 in the left eye. Anterior segment examination was unremarkable with dilated fundus examination showing a clear vitreous, tortuous blood vessel, a hyperemic disc and fibrosis at the macula. The left eye (LE) examination was unremarkable. Optical Coherence Tomography (OCT) showed fibrosis due to the previous wet AMD and hyperreflective excrescences projecting from the retinal pigment epithelium (RPE) outside of the old area of wet AMD. Fundus Fluorescein Angiogram (FFA) showed hyperfluorescent spots in a wreath-like pattern increasing in intensity in the early phase and showing late staining towards the late phase while Indocyanine green angiography (ICGA) did not clearly delineate the lesions. Fundus autofluorescence (FAF) revealed hyper Autofluorescence (AF) at the posterior pole. Optical Coherence Tomography Angiography (OCTA) revealed a flow reduction in the choriocapillaris of the affected area. Basic blood investigations with Venereal Disease Research Laboratory (VDRL), syphilitic IgM and IgG antibodies, Quantiferon TB gold test, complete renal function tests and liver function tests were performed. All the blood investigations were within normal limits and the workup for syphilis and tuberculosis was negative. The patient was started on 1mg/kg body weight of oral prednisolone (after the non-response to low dose of oral steroids) with the diagnosis of secondary multiple evanescent white dot syndrome (MEWDS) secondary to wet AMD. The patient was followed up every weekly and the last visit showed improvement in visual acuity to 20/50 with resolution of lesions on FAF and OCT macula. Conclusion and importance: Secondary MEWDS is extremely rare and unique in terms of its presentation and its association with preexisting chorioretinal disease where there is damage to the choriocapillaris- Bruch's membrane-RPE complex. This case report highlights one such rare case scenario and how multimodal imaging helps in the diagnosis, management and follow-up of patients with secondary MEWDS.

Pneumatic displacement of submacular haemorrhage secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy.

BACKGROUND: To compare the visual and anatomical outcomes of pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (VEGF) therapy versus anti-VEGF monotherapy in treatment-naive eyes with submacular haemorrhage (SMH) secondary to neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. METHODS: In a retrospective comparative interventional study of 57 eyes, the changes in logMAR visual acuity (VA), and SMH height and area at baseline at months 1, 3 and 12 were compared between the PD and non-PD groups. RESULTS: There was no significant difference in mean VA in the PD versus non-PD group at month 12 (1.1 versus 0.7, p = 0.09). At baseline, the PD group, compared to the non-PD group, had significantly larger SMH area (35.9 versus 26.9 mm2, p = 0.04) and SMH height at the fovea (733.7 versus 503.6 µm, p < 0.01). The greatest reduction in SMH height and area occurred between baseline and month 1 in the PD group, which was faster than between month 1 and month 3 in the non-PD group, with similar findings in the matched pair analysis matched for SMH height and area. In the multivariable analysis, only baseline VA was associated with VA outcomes (month 1: ß = -0.46, 95% [confidence interval] CI = -0.78 to -0.14, p = 0.006; month 3: ß = -0.52, 95% CI = -0.86 to -0.18, p = 0.004; and month 12: ß = -0.78, 95% CI = -1.16 to -0.39, p < 0.001). CONCLUSIONS: The visual outcome of SMH at month 12 in nAMD and PCV is poor regardless of whether PD is performed in addition to anti-VEGF therapy, although a more rapid resolution of SMH can be expected.

The economic burden of inherited retinal disease in Singapore: a prevalence-based cost-of-illness study.

OBJECTIVE: To assess the economic impact of inherited retinal disease (IRD) among Singaporeans. METHODS: IRD prevalence was calculated using population-based data. Focused surveys were conducted for sequentially enrolled IRD patients from a tertiary hospital. The IRD cohort was compared to the age- and gender-matched general population. Economic costs were expanded to the national IRD population to estimate productivity and healthcare costs. RESULTS: National IRD caseload was 5202 cases (95% CI, 1734-11273). IRD patients (n = 95) had similar employment rates to the general population (67.4% vs. 70.7%; p = 0.479). Annual income was lower among IRD patients than the general population (SGD 19,500 vs. 27,161; p < 0.0001). Employed IRD patients had lower median income than the general population (SGD 39,000 vs. 52,650; p < 0.0001). Per capita cost of IRD was SGD 9382, with a national burden of SGD 48.8 million per year. Male gender (beta of SGD 6543, p = 0.003) and earlier onset (beta of SGD 150/year, p = 0.009) predicted productivity loss. Treatment of the most economically impacted 10% of IRD patients with an effective IRD therapy required initial treatment cost of less than SGD 250,000 (USD 188,000) for cost savings to be achieved within 20 years. CONCLUSIONS: Employment rates among Singaporean IRD patients were the same as the general population, but patient income was significantly lower. Economic losses were driven in part by male patients with early age of onset. Direct healthcare costs contributed relatively little to the financial burden.

Initial experiences of switching to faricimab for neovascular age-related macular degeneration and polypoidal choroidal vasculopathy in an Asian population.

Purpose: To describe the early experiences of patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) whose treatment was switched to faricimab from other anti-vascular endothelial growth factor (VEGF) agents. Methods: This is a prospective cohort of eyes with nAMD and PCV that were previously treated with anti-VEGF agents other than faricimab. We evaluated visual acuity (VA), central subfield thickness (CST), macular volume (MV), pigment epithelial detachment (PED) height, and choroidal thickness (CT) after one administration of faricimab. Where present, fluid was further evaluated according to intraretinal fluid (IRF), subretinal fluid (SRF), or within PED. Results: Seventy-one eyes from 71 patients were included (45.07% PCV and 54.93% typical nAMD). The mean [standard deviation (± SD)] VA, CST, and MV improved from 0.50 logMAR (± 0.27 logMAR) to 0.46 logMAR (± 0.27 logMAR) (p = 0.20), 383.35 µm (± 111.24 µm) to 322.46 µm (± 103.89 µm (p < 0.01), and 9.40 mm3 (± 1.52 mm3) to 8.75 mm3 (± 1.17 mm3) (p < 0.01) from switch to post switch visit, respectively. The CT reduced from 167 µm (± 151 µm) to 149 µm (± 113 µm) (p < 0.01). There was also a significant reduction in the maximum PED height between visits [302.66 µm (± 217.97 µm)] and the post switch visit [236.66 µm (± 189.05 µm); p < 0.01]. This difference was greater in PEDs that were predominantly serous in nature. In the eyes with typical nAMD (n = 39), improvements were significant for CST, MV, CT, and PED. In the eyes with PCV (n = 32), only reductions in CT were statistically significant, while VA, CST, MV, and PED only showed numerically smaller improvements. One patient developed mild vitritis without vasculitis, which resolved with topical steroids with no sequelae. Conclusions: In our case series of Asian nAMD patients, switching to faricimab was associated with a stable VA and meaningful anatomical improvements, particularly with typical nAMD subtypes.

Positive-charge tuned gelatin hydrogel-siSPARC injectable for siRNA anti-scarring therapy in post glaucoma filtration surgery.

Small interfering RNA (siRNA) therapy is a promising epigenetic silencing strategy. However, its widespread adoption has been severely impeded by its ineffective delivery into the cellular environment. Here, a biocompatible injectable gelatin-based hydrogel with positive-charge tuned surface charge is presented as an effective platform for siRNA protection and delivery. We demonstrate a two-step synthesis of a gelatin-tyramine (Gtn-Tyr) hydrogel with simultaneous charge tunability and crosslinking ability. We discuss how different physiochemical properties of the hydrogel interact with siSPARC (siRNA for secreted protein, acidic and rich in cysteine), and study the positive-charge tuned gelatin hydrogel as an effective delivery platform for siSPARC in anti-fibrotic treatment. Through in vitro studies using mouse tenon fibroblasts, the positive-charge tuned Gtn-Tyr hydrogel shows sustained siSPARC cellular internalization and effective SPARC silencing with excellent biocompatibility. Similarly, the same hydrogel platform delivering siSPARC in an in vivo assessment employing a rabbit model shows an effective reduction in subconjunctival scarring in post glaucoma filtration surgery, and is non-cytotoxic compared to a commonly used anti-scarring agent, mitomycin-C. Overall, the current siRNA delivery strategy involving the positive-charge tuned gelatin hydrogel shows effective delivery of gene silencing siSPARC for anti-fibrotic treatment. The current charge tunable hydrogel delivery system is simple to fabricate and highly scalable. We believe this delivery platform has strong translational potential for effective siRNA delivery and epigenetic silencing therapy.

Repeatability of tear meniscus evaluation using spectral-domain Cirrus® HD-OCT and time-domain Visante® OCT.

PURPOSE: To investigate the intra-rater, inter-rater and inter-device repeatability of a spectral-domain OCT (Cirrus) and a time-domain OCT (Visante) for tear meniscus height (TMH) and area (TMA) measurements. METHODS: 20 participants with no known eye disease were recruited. Both eyes of participants were imaged with both OCTs under the similar conditions. The inferior tear meniscus was imaged at 6 o'clock position whereas the superior meniscus was imaged at 12 o'clock position. Data from the right eyes was analyzed. Two raters independently measured TMH and TMA using the OCT images, and one rater repeated the measurements. Intra-rater, inter-rater and inter-device repeatability of measurements were assessed using Bland-Altman plots and pooled standard deviation. RESULTS: For intra-rater repeatability, TMH and TMA measurements were more repeatable in Cirrus than Visante (95% limits of agreement (LOA): TMH (µm), -22 to 66 (Cirrus), -125 to 45 (Visante); TMA (µm(2)), -1632 to 5331 (Cirrus), -38,050 to 21,874 (Visante)). For inter-rater agreement, TMH and TMA were also more repeatable in Cirrus than Visante (95%LOA: TMH (µm), -29 to 107 (Cirrus), -215 to 252 (Visante); TMA (µm(2)), -6650 to 9567 (Cirrus), -33,119 to 39,272 (Visante)). Inter-device agreement was poor (95%LOA: TMH (µm), -158 to 150; TMA (µm(2)), -32,903 to 14,076). There was no significant difference in inferior TMH between Cirrus and Visante (p>0.05). Inferior TMA was significantly lower in Cirrus by a mean difference of 10,223µm(2) (95% confidence interval, 5479, 14,966) (p=0.0002). CONCLUSION: Spectral-domain OCT is superior to time-domain OCT for intra-rater and inter-rater repeatability of TMH and TMA measurements.

A Survey on the Preference of Sustained Glaucoma Drug Delivery Systems by Singaporean Chinese Patients: A Comparison Between Subconjunctival, Intracameral, and Punctal Plug Routes.

PURPOSE: To investigate the acceptance and preferences rates of 3 sustained drug delivery systems in glaucoma patients. MATERIALS AND METHODS: A cross-sectional study involving 250 Chinese patients recruited from outpatient glaucoma clinics in Singapore using an interviewer-administered survey. Beliefs toward medicines, eye drops, illness perception, medication adherence, and health literacy were assessed using validated questionnaires. After receiving standard information on the 3 sustained drug delivery systems, that is, subconjunctival, intracameral, and punctal routes; each route's acceptance and attitudes were determined. RESULTS: The subconjunctival (acceptance: 61.6%, n=154), intracameral (acceptance: 57.2%, n=143), and punctal (acceptance: 63.2%, n=158) routes were willing to be accepted by the majority of the interviewed patients. Among those, 78.6%, 79.1%, and 78.5% were willing to pay an equal or higher cost compared with their current eye drops for the subconjunctival, intracameral, and punctal plug routes, respectively. Independent factors associated with the acceptance for subconjunctival, intracameral, and punctal plug routes included: male sex (P=0.007, 0.014, 0.046, respectively), patients not on health care subsidies (P=0.022, 0.002, 0.016, respectively), and bilateral glaucoma disease (P=0.003, 0.013, 0.004, respectively). A total of 120 (48.0%) patients ranked punctal plug placement as the preferred route for sustained drug delivery followed by subconjunctival (n=76, 30.4%) and intracameral (n=54, 21.6%) routes. CONCLUSIONS: Sustained drug delivery for the medical treatment of glaucoma is an acceptable alternative to daily eye drop administration by most Singaporean Chinese individuals in this study. Male patients, nonsubsidized patients, and those with bilateral glaucoma were independently associated with preference of these 3 alternative routes of administration to traditional glaucoma drops.