Nirodhini Narendran

Ranibizumab in myopic choroidal neovascularization: the 12-month results from the REPAIR study

pathophysiology in LHON. In this study, we reported that ganglion cell analysis could precisely detect the loss of retinal ganglion cell in a time-dependent manner during early phase of LHON when RNFL thickness had not decreased yet. We also raise the possibility that there might be many more patients>60 years of age with visual loss owing to LHON than we have supposed previously. It may be worth investigating mtDNA point mutations regardless of age if a patient presents with unknown visual acuity loss with central scotoma.

Safety of Intravitreal Ocriplasmin for Focal Vitreomacular Adhesion in Patients with Exudative Age-Related Macular Degeneration

PURPOSE The evaluation of the safety and preliminary efficacy of 125 μg ocriplasmin intravitreal injection in patients with focal vitreomacular adhesion (VMA) and exudative age-related macular degeneration (AMD). DESIGN Randomized, sham-injection controlled, double-masked, multicenter, phase II trial. PARTICIPANTS A total of 100 patients with VMA and wet AMD were randomized 3:1 to receive 125 μg ocriplasmin intravitreal injection or sham injection. METHODS Study treatment was administered in the mid-vitreous cavity by injection. Post-treatment safety and efficacy assessments were made at baseline and on days 7, 14, and 28 and months 3, 6, and 12 after injection. Secondary efficacy end points were exploratory in nature. MAIN OUTCOME MEASURES The safety and tolerability of ocriplasmin were evaluated. The primary efficacy end point was the proportion of patients with VMA release at day 28 after injection. Secondary end points reported included VMA release over time, total posterior vitreous detachment (PVD), change in visual acuity from baseline, and number of anti-vascular endothelial growth factor (VEGF) injections. RESULTS The safety of ocriplasmin in patients with VMA and wet AMD was shown to be comparable to the known safety profile, with the majority of adverse events in the study eye occurring in the first 7 days after study treatment. A greater proportion of patients achieved VMA resolution and total PVD at month 12 with ocriplasmin compared with sham treatment. There was a decrease in the number of anti-VEGF injections with ocriplasmin at month 12 compared with the sham group, although no differences in visual acuity were observed. CONCLUSIONS Ocriplasmin treatment in this population seems to be generally safe and well tolerated and resulted in more patients achieving VMA resolution and PVD with less anti-VEGF use compared with sham treatment.

A Case of Candida albicans Endophthalmitis with No Predisposing Risk Factors and a Distant Source of Infection

Purpose: To report a case of Candida albicans endophthalmitis with no identifiable predisposing risk factors. Case Report: A 57-year-old male presented with a 3-day history of worsening floaters and reduced visual acuity. Fundoscopy and optical coherence tomography showed presence of fluffy white preretinal and intraretinal infiltrates. With no past medical history or evidence of immunosuppression but having travelled abroad and suffered from diarrhoea, fungal aetiology was thought to be unlikely and as a result, treatment was commenced for toxoplasma. Despite treatment, his vision did not improve. Initial investigations including inflammatory markers, serology for toxoplasmosis, blood culture, chest radiograph and aqueous sampling could not identify a source of infection. However, polymerase chain reaction results from vitreous sampling revealed C. albicans. As a result, the patient was treated with intravenous voriconazole and intravitreal amphotericin B. As initial clinical improvement was limited, a vitrectomy was performed with further intravitreal amphotericin B. Clinical improvement was rapid following vitrectomy. After repeated Gram staining and culture of infected toenails, Gram-positive yeast cells were isolated. Conclusion: Although C. albicans is a frequent cause of endogenous endophthalmitis, patients often have one or more predisposing systemic condition assisting the diagnosis. The present case illustrates that (1) even in the absence of any predisposing risk factors, C.albicans should be considered as a possible differential diagnosis in recalcitrant uveitis, and (2) endogenous candida endophthalmitis can be a result of fungal infections from distant sites such as the toenails.

Bilateral visual outcomes and service utilization of patients treated for 3 years with ranibizumab for neovascular age-related macular degeneration

Background The aim of this study was to describe bilateral visual outcomes and the effect of incomplete follow-up after 3 years of ranibizumab therapy for neovascular age-related macular degeneration. Secondarily, the demands on service provision over a 3-year period were described. Methods Data on visual acuity, hospital visits, and injections were collected over 36 months on consecutive patients commencing treatment over a 9-month period. Visual outcome was determined for 1) all patients, using last observation carried forward for missed visits due to early discontinuation and 2) only those patients completing full 36-month follow-up. Results Over 3 years, 120 patients cumulatively attended hospital for 1,823 noninjection visits and 1,365 injection visits. A visual acuity loss of <15 letters (L) was experienced by 78.2% of patients. For all patients (n=120), there was a mean loss of 1.68 L using last observation carried forward for missing values. Excluding five patients who died and 30 who discontinued follow-up, mean gain was 1.47 L. In bilateral cases, final acuity was on average 9 L better in second eyes compared to first eyes. Also, 91% of better-seeing eyes continued to be the better-seeing eye. Conclusion We have demonstrated our approach to describing the long-term service provision and visual outcomes of ranibizumab therapy for neovascular age-related macular degeneration in a consecutive cohort of patients. Although there was a heavy burden with very frequent injections and clinic visits, patients can expect a good level of visual stability and a very high chance of maintaining their better-seeing eye for up to 3 years.

Differences in the topographic profiles of retinal thickening in eyes with and without serous macular detachment associated with diabetic macular oedema.

Purpose To investigate if cases of diabetic macular oedema (DMO) associated with serous macular detachment (SMD) have a different topographic profile of retinal thickening compared with DMO cases not associated with SMD. Methods Optical coherence tomography scans of 152 eyes from 152 patients with centre-involving DMO and central subfield thickness >350 µm were identified. Measurements were taken of the neural retina at the highest point of thickening within the central subfield (H) and lateral extent of retina thicker than 350 µm (W). Group means were compared between eyes with SMD and eyes without SMD. Results SMD was present in 55 eyes (36%). H was lower in eyes with SMD than in eyes without SMD (396 µm vs 550 µm, p<0.001) while W was higher in eyes with SMD compared with eyes without SMD (4.74 mm vs 4.18 mm, p=0.011). Conclusions There were distinct differences in topographical profiles of retinal thickening between eyes with SMD and eyes without SMD. These findings suggest a possible mechanical basis for the pathogenesis of SMD in DMO.

Ocular surface effects of repeated application of povidone iodine in patients receiving frequent intravitreal injections

Abstract Background: The aim of this study was to investigate the patient reported symptoms and objective signs of tear film and ocular surface abnormalities experienced by patients undergoing repeated exposure to povidone iodine as a consequence of requiring frequent intravitreal injections for wet macular degeneration. Methods: This was a prospective study of consecutive patients who had received recent povidone 5% solution for sterile preparation of intravitreal injection less than 3 months prior to inclusion with a total of at least 3 intravitreal injections for macular degeneration. Each patient had one study eye which was undergoing regular intravitreal injection and a fellow eye which was not undergoing any injections. Each patient underwent evaluations of various tear film parameters on a single occasion for both eyes. The primary outcome was severity of dry eye symptoms as measured by the Schein dry eye questionnaire. The secondary outcomes were tear film osmolarity and corneal punctate staining using the Oxford Grading Scale. Results: A total of 90 patients were included in the study. 43.3% n = 39, were using ocular lubricating medication on a regular basis. A significantly greater proportion of study eyes had a Schein dry eye questionnaire score of 7 or higher; 12.2%, n = 11 amongst study eyes vs 4.4%, n = 4 amongst control, fellow eyes (p < 0.05). In terms of secondary outcomes, the study eyes had a slightly higher mean tear film osmolality compared to control, fellow eyes: 305.5 ± 1.7 in study eyes vs 302 ± 1.6 in control eyes although this difference was not statistically significant (p = 0.087). The study eyes had statistically significantly worse corneal staining as determined by the Oxford grading scale; 0.69 in study eyes vs 0.58 in control, fellow eyes (p = 0.02). Conclusion: Our results confirm the detrimental impact of repeated application of povidone iodine for intravitreal injection procedures on symptoms of dry eyes as experienced and reported by patients.

Clinical efficacy and safety of a light mask for prevention of dark adaptation in treating and preventing progression of early diabetic macular oedema at 24 months (CLEOPATRA): a multicentre, phase 3, randomised controlled trial

Summary Background We aimed to assess 24-month outcomes of wearing an organic light-emitting sleep mask as an intervention to treat and prevent progression of non-central diabetic macular oedema. Methods CLEOPATRA was a phase 3, single-blind, parallel-group, randomised controlled trial undertaken at 15 ophthalmic centres in the UK. Adults with non-centre-involving diabetic macular oedema were randomly assigned (1:1) to wearing either a light mask during sleep (Noctura 400 Sleep Mask, PolyPhotonix Medical, Sedgefield, UK) or a sham (non-light) mask, for 24 months. Randomisation was by minimisation generated by a central web-based computer system. Outcome assessors were masked technicians and optometrists. The primary outcome was the change in maximum retinal thickness on optical coherence tomography (OCT) at 24 months, analysed using a linear mixed-effects model incorporating 4-monthly measurements and baseline adjustment. Analysis was done using the intention-to-treat principle in all randomised patients with OCT data. Safety was assessed in all patients. This trial is registered with Controlled-Trials.com, number ISRCTN85596558. Findings Between April 10, 2014, and June 15, 2015, 308 patients were randomly assigned to wearing the light mask (n=155) or a sham mask (n=153). 277 patients (144 assigned the light mask and 133 the sham mask) contributed to the mixed-effects model over time, including 246 patients with OCT data at 24 months. The change in maximum retinal thickness at 24 months did not differ between treatment groups (mean change −9·2 μm [SE 2·5] for the light mask vs −12·9 μm [SE 2·9] for the sham mask; adjusted mean difference −0·65 μm, 95% CI −6·90 to 5·59; p=0·84). Median compliance with wearing the light mask at 24 months was 19·5% (IQR 1·9–51·6). No serious adverse events were related to either mask. The most frequent adverse events related to the assigned treatment were discomfort on the eyes (14 with the light mask vs seven with the sham mask), painful, sticky, or watery eyes (14 vs six), and sleep disturbance (seven vs one). Interpretation The light mask as used in this study did not confer long-term therapeutic benefit on non-centre-involving diabetic macular oedema and the study does not support its use for this indication. Funding The Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research partnership.

Clinical characteristics and selection of treatment modality for patients with vitreomacular traction: real-world implementation of NICE guidance (TA297).

Aim To investigate the qualitative aspects in patient selection and the quantitative impact of disease burden in real world treatment of vitreomacular traction (VMT) and implementation of the National Institute for Health and Care Excellence (NICE) guidance (TA297). Methods A monocentric, retrospective review of consecutive patients undergoing optical coherence tomography (OCT) imaging over a 3 month period. Patients with VMT in at least one eye were identified for further data collection on laterality, visual acuity, symptoms, presence of epiretinal membrane, macular hole and treatment selection. Results A total of 3472 patients underwent OCT imaging with a total of 6878 eyes scanned. Out of 87 patients, 74 patients had unilateral VMT (38 right, 36 left) and 13 patients had bilateral VMT. Eighteen patients with unilateral VMT satisfied NICE criteria of severe sight problems in the affected eye. Eight were managed for a coexisting pathology, one refused treatment, one patient did not attend, two closed spontaneously, and one received ocriplasmin prior to the study start date. Only two patients with unilateral VMT received ocriplasmin and three underwent vitrectomy. Those failing to meet NICE criteria for unilateral VMT were predominantly asymptomatic (n=49) or had coexisting ERM (n=5) or both (n=2). Conclusion Ocriplasmin provides an alternative treatment for patients with symptomatic VMT. Our data shows that the majority of patients with VMT do not meet NICE TA297 primarily due to lack of symptoms. Those meeting NICE criteria, but not treated, tended to have coexisting macular pathology. Variation in patient selection due to subjective factors not outlined in NICE guidance suggests that real world outcomes of ocriplasmin therapy should be interpreted with caution.

Ensuring that mandatory guidance is being correctly implemented – experience of using the NICE technology appraisal audit tool from TA155

Correspondence: Nirodhini Narendran Wolverhampton and Midland Counties Eye Infirmary, Wolverhampton Hospitals NHS Trust, Wednesfield Road, West Midlands, WV10 0QP, UK Tel +44 19 0269 5845 Email niro.narendran@nhs.net Background: The National Institute for Clinical Excellence (NICE) Guidance TA155 for the treatment of wet age-related macular degeneration was issued in August 2008. In this work we describe our experience in the application of an audit tool for auditing the implementation of this guidance in our hospital setting and report on the specific and wider aspects of auditing guidance implementation. Method: Case notes of patients were retrospectively reviewed for compliance to the NICE Guidance TA155, using the audit tool provided, which investigated five domains. A full audit cycle was completed. Results: Our initial audit failed to reach a satisfactory level of compliance with NICE Guidance TA155 in one domain, which related to dissemination of patient information and documentation of treatment eligibility. To address this issue, we introduced specific changes to our processes, and on reaudit, were able to achieve a satisfactory level of compliance in all criteria. Conclusion: Audits on implementation of NICE guidance have not been widely reported in the clinical governance literature due to the specific relevance to individual departments. Our experience has demonstrated not only the usefulness of the audit tool in ensuring that our service was in adherence with NICE guidance but also, that as a result of introducing changes to ensure compliance, the quality of service provided to patients was further improved. Implementation of NICE guidance is an intrinsic part of the clinical governance process, and audits on the implementation of NICE guidance are requirements of all service providers, to ensure that there is uniform and systematic uptake of evidence-based medicine throughout the National Health Service.