Defining the limits of normal conjunctival fornix anatomy in a healthy South Asian population

PURPOSE: Quantifying the extent of conjunctival fibrosis for documentation of progression in conjunctival scarring disease is a clinical challenge. Measurement of forniceal foreshortening facilitates monitoring of these disorders. This study aims (1) to define the limits of the normal human conjunctival fornices and how these alter with age and (2) to provide normative data for upper and lower fornix depths (FDs) and fornix intercanthal distance (FICD) within a healthy South Asian, racially distinct population. DESIGN: Epidemiologic, cross-sectional study. PARTICIPANTS: A total of 240 subjects with national origins from South Asia, with no known ocular history and normal adnexal and conjunctival examination, aged 20 to 80 years. METHODS: An FICD modification of a custom-designed fornix depth measurer (FDM) was validated and used for measurement of both lower and upper FDs together with FICDs in 480 healthy eyes with no ocular comorbidities. Data were analyzed using repeated-measures analysis of variance and presented as means with 95% confidence intervals (CIs). MAIN OUTCOME MEASURES: Mean lower and upper FDs and FICD for the entire cohort, stratified according to age decade and sex. RESULTS: For this South Asian population, the overall upper and lower FDs were 15.3 mm (95% CI, 14.9–15.6) and 10.9 mm (95% CI, 10.7–11.1), respectively, with FICD defined as 32.9 mm (95% CI, 32.5–33.4) (upper) and 31.7 mm (95% CI, 31.3–32.1) (lower). With increasing age, a progressive reduction of all measured parameters (P < 0.001) was noted, with female subjects having significantly shallower fornices (upper FD, P < 0.001; lower FD, P < 0.001; upper FICD, P = 0.081; and lower FICD, P = 0.015). CONCLUSIONS: This is the first study to define the limits of normal upper FD and FICDs in any population group. Our study demonstrates sex variations and progressive conjunctival shrinkage with age. Although it provides important, objective data for normal forniceal anatomy, further study is recommended in other populations to confirm the generalizability of these data or to enable normal comparative datasets for the assessment of conjunctival scarring disorders among all anthropological groups

Risdiplam in Patients Previously Treated with Other Therapies for Spinal Muscular Atrophy: An Interim Analysis from the JEWELFISH Study

Introduction: Risdiplam is a survival of motor neuron 2 (SMN2) splicing modifier for the treatment of patients with spinal muscular atrophy (SMA). The JEWELFISH study (NCT03032172) was designed to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of risdiplam in previously treated pediatric and adult patients with types&nbsp;1–3 SMA. Here, an analysis was performed after all patients had received at least 1&nbsp;year of treatment with risdiplam. Methods: Patients with a confirmed diagnosis of 5q-autosomal recessive SMA between the ages of 6&nbsp;months and 60&nbsp;years were eligible for enrollment. Patients were previously enrolled in the MOONFISH study (NCT02240355) with splicing modifier RG7800 or treated with olesoxime, nusinersen, or onasemnogene abeparvovec. The primary objectives of the JEWELFISH study were to evaluate the safety and tolerability of risdiplam and investigate the PK after 2&nbsp;years of treatment. Results: A total of 174 patients enrolled: MOONFISH study (n = 13), olesoxime (n = 71 patients), nusinersen (n = 76), onasemnogene abeparvovec (n = 14). Most patients (78%) had three SMN2 copies. The median age and weight of patients at enrollment was 14.0&nbsp;years (1–60&nbsp;years) and 39.1&nbsp;kg (9.2–108.9&nbsp;kg), respectively. About 63% of patients aged 2–60&nbsp;years had a baseline total score of less than 10 on the Hammersmith Functional Motor Scale–Expanded and 83% had scoliosis. The most common adverse event (AE) was upper respiratory tract infection and pyrexia (30 patients each; 17%). Pneumonia (four patients; 2%) was the most frequently reported serious AE (SAE). The rates of AEs and SAEs per 100 patient-years were lower in the second 6-month period compared with the first. An increase in SMN protein was observed in blood after risdiplam treatment and was comparable across all ages and body weight quartiles. Conclusions: The safety and PD of risdiplam in patients who were previously treated were consistent with those of treatment-naïve patients