DELAYED FOLLOW-UP IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATED UNDER UNIVERSAL HEALTH COVERAGE: Risk Factors and Visual Outcomes.

BACKGROUND/PURPOSE: To report the rate of delayed follow-up visits (DFU), to identify risk factors of DFU, and to assess the impact of DFU on outcomes in neovascular age-related macular degeneration. METHODS: This retrospective study included all patients with neovascular age-related macular degeneration (n = 1,291) treated with antivascular endothelial growth factor injections between January 2013 and December 2020 in 2 centers in Quebec, Canada. A DFU was defined as a delay of ≥4 weeks than scheduled. Visual outcomes, especially ≥15 letters loss, were reported. RESULTS: A total of 351 patients (27.2%) experienced ≥1 DFU. Odds were greater among older patients ( P = 0.005), patients treated at the hospital rather than the clinic ( P < 0.001), and patients with worse initial visual acuity ( P = 0.024). A DFU was associated with a mean visual acuity loss of 4.2 ± 13.4 letters ( P < 0.001) and an increased incidence of intraretinal fluid and subretinal fluid ( P = 0.001, P = 0.005) at 6 months despite resumption of injections. Central foveal thickness increased after DFU but returned to pre-DFU visit at 6 months. CONCLUSION: The DFU rate in patients with neovascular age-related macular degeneration treated under a universal health care system was around 27%. Delayed follow-up visits caused significant decreases in visual acuity and increases in intraretinal fluid and subretinal fluid on optical coherence tomography that did not recover after injections resumption despite normalization of central foveal thickness.

Fear Associated with COVID-19 in Patients with Neovascular Age-Related Macular Degeneration.

PURPOSE: Since the beginning of the COVID-19 pandemic, news related to the pandemic has created a feeling of fear, particularly among high-risk groups including elderly patients. This study aimed to assess the fear associated with COVID-19 and to evaluate the fear of vision decrease related to the delay of treatment in neovascular age-related macular degeneration patients (nAMD) during the pandemic. PATIENTS AND METHODS: This is a prospective cross-sectional study of 160 actively treated patients with nAMD enrolled between September and November 2020 at a tertiary hospital in Québec, Canada. For each participant, demographic and clinical data were collected. The anxiety was rated in a questionnaire composed of two sections: the Fear of COVID-19 Scale (FCV-19S) and eight additional questions to assess ophthalmology-related COVID-19 statements. RESULTS: The mean ± standard deviation level of FCV-19S was 17.05±4.38. In the multivariable analysis, it was significantly higher in women (p<0.001) and lower in patients with a high school education vs elementary school (p=0.009). In the ophthalmology-related statements, 16% feared vision loss because of difficulties in maintaining regular follow-ups during the pandemic. The female gender was significantly associated with a higher tendency to postpone their appointment (p=0.03). No association was found between the patients' underlying disease characteristics and higher fear of vision loss. CONCLUSION: Despite the massive impact of the pandemic, anxiety related to COVID-19 and delaying ophthalmology treatments remained relatively low in nAMD patients. Greater explanations to address this fear may reduce anxiety level, especially among female patients and those with an elementary school education.

Transconjunctival suturing of the scleral flap for overfiltration with hypotony maculopathy after trabeculectomy.

OBJECTIVE: To assess the efficacy of transconjunctival suturing of the scleral flap in improving hypotony maculopathy resulting from overfiltration after trabeculectomy. DESIGN: Retrospective review. PARTICIPANTS: 35 eyes of 33 patients. METHODS: Patients underwent transconjunctival scleral flap suturing for hypotony maculopathy following trabeculectomy using mitomycin C. The scleral flap was sutured through the conjunctiva as an outpatient clinic procedure using a spatulated needle with a 10-0 nylon suture. RESULTS: The average age of the patients was 67.5 (SD 4.80, range 39-83) years, and 52% patients were male. The average duration of hypotony prior to transconjunctival suturing of the flap was 108.0 (SD 68.3) days. The median intraocular pressure (IOP) before suturing was 3 mm Hg, and the median IOP 6 months after the procedure was 9 mm Hg (p < 0.0001). The median best-corrected visual acuity (BCVA) before transconjunctival suturing of the scleral flap was 20/100, and the median BCVA 6 months after the procedure was 20/30 (p < 0.0001). Compared with visual acuity before suturing the average gain in BCVA was 4.9 (SD 0.8) lines. CONCLUSIONS: Transconjunctival suturing of the trabeculectomy scleral flap is an effective treatment to raise IOP and improve visual loss from hypotony maculopathy after trabeculectomy with overfiltering blebs.

Functional analysis of the glaucoma-causing TIGR/myocilin protein: integrity of amino-terminal coiled-coil regions and olfactomedin homology domain is essential for extracellular adhesion and secretion.

TIGR/MYOC mutations account for 2-4% of the primary open-angle glaucoma (POAG) patients. More than 90% of the known mutations are located within its carboxy-terminus olfactomedin-homology (Olf) domain (amino acids (aa) 245-504). In vitro and in vivo studies showed that several Olf domain mutations prevented myocilin secretion. To investigate if intracellular sequestration was a characteristic feature shared by a majority of the mutations, we analyzed the secretion status of 36 myocilin variants. These encompassed 26 glaucoma-causing mutations and 10 non-disease associated or undefined polymorphisms. As several variants were found to be secreted, we tested for their adhesion to the extracellular matrix (ECM) and/or cell surface. Myocilin variants were generated by site-directed mutagenesis of a vector encoding the human MYOC cDNA. COS-7 or immortalized human trabecular meshwork cells were transfected with wild-type or mutated MYOC constructs. Myocilin levels were estimated by immunoprecipitation and/or immunoblotting. All variants showed identical behaviors in both cell lines; the truncated R46X polypeptide being the only variant which could not be detected in our assays. Of the 35 variants monitored, 20 remained sequestered intracellularly. All of them encoded disease-causing polypeptides carrying Olf domain mutations. Of the 15 variants secreted into the culture medium, six (6) were POAG mutants (of which three (3) located within the Olf domain) while the remaining nine (9) were non-disease causing or undefined polymorphisms. Three (3) of the six (6) secreted mutations caused familial POAG; these were the R126W, T377M and A427T mutants. Both, the T377M and A427T mutants located within the Olf domain. When cells were cultured at 30 degrees C, a process known to facilitate protein folding, 11 of the 20 sequestered mutants were released in the extracellular medium. Out of the 15 secreted variants tested for their adhesion to the ECM and/or cell surface, only the R82C and L95P polypeptides displayed loss of their adhesive properties. Deletion experiments revealed that the coiled-coil (aa 78-105) and leucine zipper (aa 114-183) motifs were essential for adhesion. These experiments demonstrate that intracellular sequestration might be the primary mechanism contributing to myocilin-related POAG as it was associated with more than 80% of the disease-causing mutants tested in our study. A second mechanism may involve abnormal interaction(s) between myocilin and ECM and/or cell surface proteins. Our data further revealed the importance of the olfactomedin-homology domain for myocilin secretion and the significant role of the N-terminal region for its extracellular interactions.