Validity of the French version of Catquest-9SF and use of an electronic notepad for entering patient-reported outcome measures.

BACKGROUND: The Catquest-9SF questionnaire is a patient reported outcome measure that quantifies the visual benefits from cataract surgery. The purpose of this study was to translate and adapt the Catquest-9SF questionnaire for France, to assess its psychometric properties via Rasch analysis, and to assess its validity when completed using an electronic notepad. METHODS: The Catquest-9SF questionnaire was translated following the guidelines of the International Society for Pharmacoeconomics and Outcomes Research. Catquest-9SF and clinical data were collected from patients before and after routine cataract surgery. All questionnaire data were collected via an electronic notepad. Rasch analysis was performed to assess psychometric properties, and sensitivity to change was analysed for patients with complete paired pre- and post-operative questionnaires. RESULTS: A complete filled-in preoperative questionnaire was obtained for 848 patients. Rasch analysis showed good precision (person separation: 2.32, person reliability: 0.84), ordered category probability curves, no item misfit, and unidimensionality. The respondents were slightly more able than the level of item difficulty (targeting: -1.12 logits). Sensitivity was analysed on 211 paired questionnaires, and the postoperative questionnaires showed a clear ceiling effect. The effect size was 2.6. The use of an electronic notepad for completing the questionnaire worked out very well after some adjustments. CONCLUSIONS: The French version of Catquest-9SF has good psychometric properties and is suitable for use in French-speaking patients. The use of the Catquest-9SF questionnaire in an electronic format showed good validity.

Predictive values of initial semi-quantitative assessment of relative afferent pupillary defect for neovascularization in central retinal vein occlusion.

PURPOSE: To measure the predictive values of relative afferent pupillary defect (RAPD) assessed semi-quantitatively, and visual acuity (VA) at onset of central retinal vein occlusion (CRVO), for neovascularization. METHODS: Retrospective analysis of the TROXHEMO trial that included patients with CRVO within 30 days after the onset. Inclusion criteria were as follows: semi-quantitative RAPD assessment at diagnosis and/or at one month. RAPD was 'severe' if ≥ 0.9 log. Exclusion criteria were as follows: prophylactic panretinal photocoagulation (PRP) before neovascularization. RESULTS: Among the 119 patients enrolled in the main centre, 101 were analysed. 26 had a neovascular complication during the twelve months of follow-up: rubeosis (19), glaucoma (7) and posterior neovascularization (15). The mean time to onset of a neovascular complication was 4.7 months (1 to 12, median 3 months). All the patients who had a neovascular complication had RAPD at first examination or at one month (negative predictive value (NPV) = 100%) but the positive predictive value (PPV) was low (31%, 95% CI [21%; 42%]). The association 'severe RAPD or VA < 35 letters (ETDRS) at inclusion or at one month' was the best compromise between PPV (53%, [39%; 68%]) and NPV (96%, [92%; 100%]). CONCLUSION: To predict neovascularization, RAPD should be routinely evaluated with filters: the risk of neovascular complication is (a) almost nil if there is no RAPD, (b) very low if there is no severe RAPD and if VA is higher than 35 letters, and (c) higher than 50% if RAPD is ≥ 0.9 log or if VA is less than 35 letters.

[Gene therapy for retinitis pigmentosa]. / La thérapie génique des rétinites pigmentaires héréditaires.

Retinitis pigmentosa is the most common blinding inherited retinal dystrophy. Gene therapy is a burgeoning revolutionary approach that paves the way to treatment of previously incurable diseases. At the end of 2017 and 2018, a gene therapy, Luxturna®, obtained a marketing authorization by respectively the FDA (Food and Drug Administration) and the EMA (European Medicines Agency). This treatment, with proven efficacy, is available to patients with Leber congenital amaurosis and retinitis pigmentosa associated with bi-allelic mutations of the RPE 65 gene. In this paper, we present the current advances in gene therapy for retinitis pigmentosa and discuss the technological, economic and ethical challenges to overcome for gene therapy to improve medical practices.

TITLE: La thérapie génique des rétinites pigmentaires héréditaires. ABSTRACT: Les rétinites pigmentaires, ou dystrophies rétiniennes héréditaires, sont des maladies dégénératives cécitantes d'origine génétique. La thérapie génique est une approche révolutionnaire en plein essor qui ouvre la voie au traitement de maladies jusqu'ici incurables. Une thérapie génique, le Luxturna®, a obtenu une autorisation de mise sur le marché par la FDA (Food and Drug Administration) fin 2017 et l'EMA (European Medicines Agency) fin 2018. Ce traitement, à l'efficacité démontrée, destiné aux patients porteurs d'une amaurose congénitale de Leber ou d'une rétinopathie pigmentaire en lien avec une mutation bi-allélique du gène RPE65, apporte beaucoup plus de questions que de réponses. Nous présentons, dans cette revue, les avancées actuelles, puis les défis technologiques, économiques et éthiques à surmonter pour que la thérapie génique améliore nos pratiques médicales.

Comparison of two techniques used in routine care for the treatment of inflammatory macular oedema, subconjunctival triamcinolone injection and intravitreal dexamethasone implant: medical and economic importance of this randomized controlled trial.

BACKGROUND: Whether they are injected peri- or intraocularly, corticosteroids are still essential tools in the therapeutic arsenal for treating inflammatory macular oedema. A few years ago, however, only triamcinolone acetonide was available to ophthalmologists. While this compound was initially developed for rheumatological or dermatological use, it has been increasingly deployed in ophthalmology, despite still being off-label. In 2011, the system for delivery of dexamethasone from a biodegradable, injectable implant into the vitreous cavity obtained approval for use in inflammatory macular oedema. While the efficacy and safety of triamcinolone in macular oedema, including inflammatory oedema, have already been studied, there are currently no publications on subconjunctival triamcinolone injections, which are simple, effective and well tolerated. To date, the dexamethasone 700 µg implant has been authorized for the treatment of noninfectious intermediate and posterior uveitis, but there have been no studies to evaluate the efficacy and safety of the different peri- and intraocular strategies, including the treatment of inflammatory macular oedema. METHODS: This protocol is therefore designed to compare the efficacy and safety of peri- and intraocular corticosteroid injections in the treatment of inflammatory macular oedema. In this ongoing study, 142 patients will be included, and the oedematous eye will be randomised to treatment with either subconjunctival triamcinolone injection or an intravitreal implant containing 700 µg dexamethasone. Follow-up is planned for 6 months with monthly visits. Each visit will include visual acuity measurement, a slit lamp examination, fundoscopy, intraocular pressure measurement, laser flare measurement (if available) and spectral domain optical coherence tomography. DISCUSSION: The results of this trial will have a real impact on public health if it is shown that a Kenacort retard® (i.e. triamcinolone) injection costing just €2.84 and performed in the physician's office (with no additional overhead costs) is at least as effective as the dexamethasone 700 µg implant (Ozurdex®; costing approximately €960 with the injection performed in a dedicated room), with no increased side effects. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02556424. Registered on 22 September 2015.

Assessment of choroidal topographic changes by swept source optical coherence tomography after photodynamic therapy for central serous chorioretinopathy.

PURPOSE: To investigate the relationship between choroidal thickness and angiographic abnormalities in central serous chorioretinopathy (CSC) eyes by swept-source optical coherence tomography (swept-OCT), before and after half-fluence photodynamic therapy (PDT). DESIGN: Prospective interventional case series. METHODS: Consecutive patients presenting with treatment-naive active CSC underwent a complete ophthalmologic examination, including swept-OCT at study entry and at 7 days and 30 days after treatment with half-fluence PDT. The main outcome measures were changes in choroidal maps after PDT (mean ± SD) and the relationship between choroidal thickness and angiographic abnormalities. RESULTS: Of 12 patients (2 females, 10 males; mean age, 55.6 ± 14.0 years), 12 eyes were included. At study entry, mean choroidal thickness measured in the center of the fovea was significantly thicker in the study eyes as compared to the fellow eyes (420.7 ± 107.5 µm vs 349.2 ± 109.7 µm, respectively; P = 0.016). Mean choroidal thickness in the center of the fovea significantly decreased in the study eyes at both 7 days (380.2 ± 113 µm; P = 0.005) and 30 days after PDT (362.3 ± 111 µm; P = 0.002). A similar significant choroidal thinning was recorded in each early treatment of diabetic retinopathy study (ETDRS) applied to 3D swept-OCT maps. At each time point, mean choroidal thickness was significantly thicker in sectors with than in sectors without angiographic abnormalities (421 ± 102.4 µm vs 397.6 ± 96.5 µm, P = 0.002 at study entry; 381.2 ± 106.6 µm vs 364 ± 101.2 µm, P = 0.01 at day 7; 366.3 ± 103.2 µm vs 347.2 ± 99.6 µm at day 30). CONCLUSIONS: Using swept-OCT, we demonstrated that in active CSC, choroidal thickness is increased to a greater extent in areas characterized by angiographic abnormalities. This increased choroidal thickness may persist even after PDT.

Postsurgical assessment and long-term safety of recombinant adeno-associated virus-mediated gene transfer into the retinas of dogs and primates.

OBJECTIVE: To evaluate, in dogs and primates, the short-term effects of subretinal injection and the safety of long-term recombinant adeno-associated virus (rAAV)-mediated transgene expression with respect to retinal morphology and function. METHODS: Subretinal delivery of rAAV (serotype 2, 4, or 5) was performed unilaterally in 14 beagles and 9 macaques. Postsurgical condition was evaluated during a 2-month follow-up study. Three dogs and 1 primate were examined for the long-term study. Green fluorescent protein expression was monitored by fluorescent retinal imaging. Retinal anatomy and function were assessed by angiography and electroretinography, respectively. RESULTS: Transgene expression was observed in 20 of 23 subretinally injected animals (both with and without vitrectomy). We did not detect an inflammatory response in any of the 23 treated subjects. In the long-term study, transgene expression was detected at the latest points evaluated: 36 months for the rAAV-2-injected dog, 24 months for the rAAV-4 and rAAV-5 dogs, and more than 18 months for the rAAV-4-injected primate. Angiography examinations were performed and showed no retinal abnormalities. Functional evaluation showed normal electroretinographic amplitude responses that were similar to those of the noninjected contralateral eyes. CONCLUSIONS: Subretinal injection of the rAAV vector in dogs and primates is a safe procedure with no perioperative complications and a high rate of successful retinal gene transfer. The retinal anatomy and function remained unchanged, despite persistent transgene expression up to 36 months postinjection with rAAV-2, -4, or -5. Additionally, we observed no other adverse effects, such as tumor formation due to possible insertional mutagenesis. These short- and long-term studies on rAAV transgene expression using large animals are encouraging for the prospects of ocular gene therapy applications in humans. CLINICAL RELEVANCE: These short- and long-term studies on rAAV transgene expression using large animals are encouraging for the prospects of ocular gene therapy applications in humans.