Comparison of Eylea® with Lucentis® as first-line therapy in patients with treatment-naïve neovascular age-related macular degeneration in real-life clinical practice: retrospective case-series analysis.

BACKGROUND: To identify differences between Ranibizumab and Aflibercept in treatment-naïve patients with neovascular age-related macular degeneration (nvAMD) in a real-life clinical setting. METHODS: We compared two groups of patients with a fairly similar prognosis either receiving Aflibercept or Ranibizumab within a pro re nata regimen for 1 year. Changes in visual acuity (letters) and central foveal thickness (CFT) and frequency of injections after completing the loading phase were evaluated using two separate multivariate mixed linear models. RESULTS: When correcting for baseline differences between the Aflibercept (11 eyes) and Ranibizumab (16 eyes) group, there was neither divergence in visual acuity (-0.97 letters (95 % CI. -6.06-4.12); p = 0.709), nor a significant difference in the reduction of CFT (-25.16 µm, 95 % CI; (-78.01-27.68); p = 0.351) between the two groups 1 year after treatment initiation. Also, the number of injection did not differ (0.04 (95 % CI; -0.16-0.09); p = 0.565). CONCLUSION: In contrast to health claims, treatment-naïve nvAMD, Ranibizumab and Aflibercept were equivalent in terms of functional and morphologic outcomes and number of injections when studied in real-life clinical practice.

Multiple use of preservative-free single dose unit dexamethasone 0.1% eye drops is safe within 24 hours.

BACKGROUND: Unpreserved single-dose unit (SDU) eye drops are commonly used to avoid benzalkonium chloride-related toxicity. Although intended for single use, many patients report off-label repeated use of SDUs over a prolonged period. We investigated whether repeated use of dexamethasone 0.1% SDUs in the same patient increases the bacterial contamination rate. METHODS: We prospectively enrolled patients scheduled for inpatient corneal and glaucoma surgery receiving dexamethasone 0.1% SDU four times per day from the same vial. To assess contamination rates, one drop from the vial was cultured immediately after opening the SDU (t0), 10 hours later after four drop applications (t10) and 24 hours after opening without further drop applications (t24). Conjunctival swabs were taken before and after drop application. Contamination rate was assessed with a standard clinical culturing protocol without introducing a positive control. RESULTS: 110 eyes of 109 patients were evaluated. Drops collected immediately after opening the SDU (t0) were contaminated in 9/110 cultures (8.1%). At t10, 13/110 cultures were contaminated (11.8%; p=0.267) and 11/110 at t24 (10.0%; t24 vs t0; p=1.00). In 5 of 21 cases of contaminated drops at t10 and/or t24, the same isolates were cultured from the initial conjunctival swab and the SDU. In three cases, the same bacterial species was found in consecutive samples. CONCLUSION: The contamination rate of the SDU did not increase after multiple use within 24 hours. Contamination from fingertip flora was more likely than from ocular surface flora. Reuse of dexamethasone 0.1% SDU in the same patient within 24 hours appears to be safe.

Hereditary hyperferritinemia-cataract syndrome (HHCS) presenting with iron deficiency anemia associated with a new mutation in the iron responsive element of the L ferritin gene in a Swiss family.

Hereditary hyperferritinemia-cataract syndrome (HHCS) is one of the differential diagnoses of hyperferritinemia (HF) with low or normal transferrin saturation but is usually not associated with anemia. Here, we report a case of a microcytic, hypochromic anemia with hyperferritinemia as the initial presentation of a combination of iron deficiency anemia and HHCS. The latter is an autosomal dominant disorder characterized by distinctive cataracts and HF in the absence of iron overload. Sequencing studies were carried out to look for mutations in the iron responsive element (IRE) of the L ferritin gene. A heterozygous single point mutation for a +24T to C substitution in the IRE of the L ferritin gene (=HGVS c.-176T>C) was detected which has not been described before. To evaluate the pathogenetic relevance of this new mutation, we performed family studies of parents and siblings. We could identify the father and one brother with HF, cataract, and the heterozygous +24T>C mutation. Neither the mother nor the five other siblings had HF, cataract or that mutation. We therefore conclude that this newly described heterozygous +24T>C mutation in the IRE of the L ferritin gene causes HHCS.

Comparison of macular parameters after femtosecond laser-assisted and conventional cataract surgery in age-related macular degeneration.

PURPOSE: To evaluate differences in postoperative central macular thickness, central macular volume, corrected distance visual acuity (CDVA), and number of intravitreal anti-vascular endothelial growth factor (VEGF) injections between conventional and femtosecond laser-assisted cataract surgery in wet age-related macular degeneration (AMD). SETTING: Tertiary referral center, Lucerne, Switzerland. DESIGN: Retrospective case series. METHODS: Consecutive patients with AMD and cataract were enrolled between January 2010 and December 2015. Associations between postoperative changes in central macular thickness, central macular volume, CDVA, and number of anti-VEGF injections with type of surgery were assessed statistically. RESULTS: The study comprised 140 eyes (110 patients). No differences in postoperative central macular thickness (-9.20 µm; 95% confidence interval [CI], -41.68 to 23.28; P = .576), central macular volume (-0.08 mm2; 95% CI, -0.36 to 0.19; P = .553), visual acuity (0.03 logarithm of the minimum angle of resolution; 95% CI, -0.09 to 0.15; P = .647) or postoperative number of anti-VEGF injections (0.30; 95% CI, -0.45 to 1.05; P = .427) were found between the femtosecond laser group and the conventional group over a mean follow-up of 619 days ± 473 (SD). In the 33 eyes that had optical coherence tomography measurement within a postoperative period of 2 weeks, the central macular volume was significantly lower in femtosecond laser-treated eyes (-0.71 mm2; 95% CI, -1.19 to -0.23; P = .005). CONCLUSIONS: Overall, the postoperative course between wet AMD after femtosecond laser and conventional cataract surgery was equal. During the early follow-up, femtosecond laser-treated eyes had less subclinical macular edema, indicating a possible benefit for patients with macular vulnerability.

Anti-VEGF treatment patterns and associated health care costs in Switzerland: findings using real-world claims data.

BACKGROUND: Little is known about the patterns of actual health care delivery of anti-vascular endothelial growth factor (VEGF) treatment in patients with age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion in Switzerland. The purpose of this study was to describe these treatment patterns, specifically comparing the numbers of anti-VEGF injections and associated expenditures between patients treated with ranibizumab and those treated with aflibercept in Switzerland using claims data. METHODS: We identified our study patients retrospectively using the Helsana claims database, which includes data on approximately 1.2 million subjects with basic health insurance. Patients qualified for inclusion if ranibizumab or aflibercept had been initiated between December 1, 2012 (when aflibercept was approved by the Federal Office of Public Health) and November 30, 2013. Within this set, patients with at least 12 months of continuous insurance enrolment in the previous year were considered. In univariate analyses, we examined the distribution of demographic data and patient characteristics between those receiving ranibizumab and those receiving aflibercept. Numbers of injections and associated health care expenditures observed during the 6-month follow-up period after incident treatment were the two outcomes considered. In multivariate regression analyses, controlling for possible confounding factors, we compared differences in these two outcomes between patients treated with ranibizumab and those treated with aflibercept. RESULTS: Of 3,260 patients who were on anti-VEGF treatment for an ophthalmological indication between December 1, 2012 and November 30, 2013, 1,150 qualified for inclusion. Age, geographic region, and number of physician visits in the previous year were significant factors in the number of injections given during the 6-month follow-up period. Frequency of injections and associated health care expenditures were similar between the groups when correcting for differences in patient characteristics. CONCLUSION: Contrary to the recommendations regarding frequency of injections and the results of clinical studies, aflibercept and ranibizumab are used in a similar fashion in Switzerland, resulting in similar total health care expenditures for both these anti-VEGF agents.

Comparison of Outcomes and Costs of Ranibizumab and Aflibercept Treatment in Real-Life.

BACKGROUND: Treatment efficacy and costs of anti-VEGF drugs have not been studied in clinical routine. OBJECTIVE: To compare treatment costs and clinical outcomes of the medications when adjusting for patients' characteristics and clinical status. DESIGN: Comparative study. SETTING: The largest public ophthalmologic clinic in Switzerland. PATIENTS: Health care claims data of patients with age-related macular degeneration, diabetic macula edema and retinal vein occlusion were matched to clinical and outcome data. MEASUREMENTS: Patients' underlying condition, gender, age, visual acuity and retinal thickness at baseline and after completing the loading phase, the total number of injections per treatment, the visual outcome and vital status was secured. RESULTS: We included 315 patients (19595 claims) with a follow-up time of 1 to 99 months (mean 32.7, SD 25.8) covering the years 2006-2014. Mean age was 78 years (SD 9.3) and 200 (63.5%) were female. At baseline, the mean number of letters was 55.6 (SD 16.3) and the central retinal thickness was 400.1 µm (SD 110.1). Patients received a mean number of 15.1 injections (SD 13.7; range 1 to 85). Compared to AMD, adjusted cost per month were significantly higher (+2174.88 CHF, 95%CI: 1094.50-3255.27; p<0.001) for patients with DME, while cost per month for RVO were slightly but not significantly higher. (+284.71 CHF, 95% CI: -866.73-1436.15; p = 0.627). CONCLUSIONS: Patients with DME are almost twice as expensive as AMD and RVO patients. Cost excess occurs with non-ophthalmologic interventions. The currently licensed anti-VEGF medications did not differ in costs, injection frequency and clinical outcomes. Linking health care claims to clinical data is a useful tool to examine routine clinical care.

Novel CACNA1A mutation(s) associated with slow saccade velocities.

Mutations in the voltage-gated Cav2.1 P/Q-type calcium channel (CACNA1A) can cause a wide spectrum of phenotypes, including the episodic ataxia type 2. Beside the growing number of descriptions of novel CACNA1A mutations with episodic ataxia type 2 phenotype; there are only rare reports on interictal oculomotor signs other than nystagmus. We describe a novel CACNA1A mutation and an unclassified CACNA1A in-frame variant in a Swiss family presenting as the episodic ataxia type 2 phenotype associated with reduced saccade velocity. In this case series interictal clinical examination showed only minimal neurological findings as mild limb ataxia and nystagmus, but most interestingly saccade analysis of all three affected individuals demonstrated reduced mean saccade velocity. Genetic testing of CACNA1A revealed a de novo frame-shift mutation (c.2691dupC/p.Thyr898Leufs 170) in the index patient in addition to an unclassified in-frame variant (c.6657_6659dupCCA/p.His2220dup) segregating in all three affected individuals. The de novo frame-shift CACNA1A mutation and the unclassified in-frame CACNA1A variant were associated with the episodic ataxia type 2 phenotype and reduced mean saccade velocity, which suggests involvement of brainstem or neural pathways connecting brainstem and the cerebellum in this disease.