Diabetic maculopathy: multicolour and SD-OCT versus fundus photography.

OBJECTIVE: The English Diabetic Eye Screening (DES) programme recommends patients with M1 diabetic maculopathy to be referred to hospital eye services. DES uses flash fundus photography as the reference standard for maculopathy grading. We compared multicolour versus non-stereoscopic fundus photography at identifying M1 maculopathy, with spectral domain optical coherence tomography (SD-OCT) identifying macular thickening. METHODS AND ANALYSIS: This cross-sectional study included 345 patients with R1M1 referred from DES and reviewed in secondary care with fundus photographs, multicolour and SD-OCT. Maculopathy was graded based on DES exudate criteria on both multicolour and fundus photography in a blind fashion by two independent graders. Macular thickness was ascertained on SD-OCT. RESULTS: Intergrader agreement on grading maculopathy using fundus photography (Cohen's κ=0.91) and multicolour (Cohen's κ=0.82) was 'almost perfect'. Agreement between fundus photography and multicolour on grading maculopathy (Cohen's κ=0.76) was 'substantial'. Compared with fundus photography, multicolour had sensitivity of 87% (95% CI 81% to 93%) and specificity of 90% (95% CI 87% to 94%) in detecting M1 maculopathy. SD-OCT identified 84 eyes with macular thickening, 47 of which were graded as M0 by fundus photography. 5 eyes with exudates and severe macular oedema requiring urgent intervention were also missed on fundus photography but not on multicolour. Multicolour, when complemented by SD-OCT, did not miss any clinically significant macular oedema. CONCLUSION: Multicolour integrates synergistically in a single platform with SD-OCT providing effective monitoring of M1 diabetic maculopathy. The need for fundus photography is eliminated by multicolour/SD-OCT in dedicated R1M1 virtual clinics not requiring parallel diabetic retinopathy grading.

Incomplete Retinal Pigment Epithelial and Outer Retinal Atrophy in Age-Related Macular Degeneration: Classification of Atrophy Meeting Report 4.

PURPOSE: To describe the defining features of incomplete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA), a consensus term referring to the OCT-based anatomic changes often identified before the development of complete RPE and outer retinal atrophy (cRORA) in age-related macular degeneration (AMD). We provide descriptive OCT and histologic examples of disease progression. DESIGN: Consensus meeting. PARTICIPANTS: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists. METHODS: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed longitudinal multimodal imaging of eyes with AMD. Consensus was reached on a classification system for OCT-based structural alterations that occurred before the development of atrophy secondary to AMD. New terms of iRORA and cRORA were defined. This report describes in detail the CAM consensus on iRORA. MAIN OUTCOME MEASURES: Defining the term iRORA through OCT imaging and longitudinal cases showing progression of atrophy, with histologic correlates. RESULTS: OCT was used in cases of early and intermediate AMD as the base imaging method to identify cases of iRORA. In the context of drusen, iRORA is defined on OCT as (1) a region of signal hypertransmission into the choroid, (2) a corresponding zone of attenuation or disruption of the RPE, and (3) evidence of overlying photoreceptor degeneration. The term iRORA should not be used when there is an RPE tear. Longitudinal studies confirmed the concept of progression from iRORA to cRORA. CONCLUSIONS: An international consensus classification for OCT-defined anatomic features of iRORA are described and examples of longitudinal progression to cRORA are provided. The ability to identify these OCT changes reproducibly is essential to understand better the natural history of the disease, to identify high-risk signs of progression, and to study early interventions. Longitudinal data are required to quantify the implied risk of vision loss associated with these terms. The CAM classification provides initial definitions to enable these future endeavors, acknowledging that the classification will be refined as new data are generated.

Analysis of Retinal Segmentation Changes at High Altitude With and Without Acetazolamide.

Purpose: Our aim was to assess retinal venous diameter and segmented retinal layer thickness variation in acute systemic hypoxia with and without acetazolamide and to relate these changes to high altitude headache (HAH), as a proxy for intracerebral pathophysiology. Methods: A total of 20 subjects participated in a 4-day ascent to the Margherita Hut (4,559 m) on Monte Rosa in the Italian Alps. Each participant was randomized to either oral acetazolamide 250 mg twice daily or placebo. A combination of digital imaging and optical coherence tomography was used to measure retinal vessel diameter and retinal layer thickness. Clinically-assessed HAH was recorded. Results: A total of 18 participants had usable digital and OCT images, with 12 developing HAH. Significant thickening was seen only in the two inner layers of the retina, the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) at P = 0.012 and P = 0.010, respectively, independent of acetazolamide. There was a significant positive correlation between HAH and both retinal venous diameter (T = 4.953, P = 0.001) and retinal artery diameter (T = 2.865, P = 0.015), with both unaffected by acetazolamide (F = 0.439, P = 0.518). Conclusions: Retinal venous diameter correlates positively with HAH, adding further evidence for the proposed venous outflow limitation mechanism. The inner layers of the retina swelled disproportionately when compared to the outer layers under conditions of systemic hypoxia. Acetazolamide does not appear to influence altitudinal changes of retinal layers and vasculature.

Ranibizumab 0.5 mg for Diabetic Macular Edema with Bimonthly Monitoring after a Phase of Initial Treatment: 18-Month, Multicenter, Phase IIIB RELIGHT Study.

PURPOSE: To evaluate ranibizumab 0.5 mg using bimonthly monitoring and individualized re-treatment after monthly follow-up for 6 months in patients with visual impairment due to diabetic macular edema (DME). DESIGN: A phase IIIb, 18-month, prospective, open-label, multicenter, single-arm study in the United Kingdom. PARTICIPANTS: Participants (N = 109) with visual impairment due to DME. METHODS: Participants received 3 initial monthly ranibizumab 0.5 mg injections (day 0 to month 2), followed by individualized best-corrected visual acuity (BCVA) and optical coherence tomography-guided re-treatment with monthly (months 3-5) and subsequent bimonthly follow-up (months 6-18). Laser was allowed after month 6. MAIN OUTCOME MEASURES: Mean change in BCVA from baseline to month 12 (primary end point), mean change in BCVA and central retinal thickness (CRT) from baseline to month 18, gain of ≥10 and ≥15 letters, treatment exposure, and incidence of adverse events over 18 months. RESULTS: Of 109 participants, 100 (91.7%) and 99 (90.8%) completed the 12 and 18 months of the study, respectively. The mean age was 63.7 years, the mean duration of DME was 40 months, and 77.1% of the participants had received prior laser treatment (study eye). At baseline, mean BCVA was 62.9 letters, 20% of patients had a baseline BCVA of >73 letters, and mean baseline CRT was 418.1 µm, with 32% of patients having a baseline CRT <300 µm. The mean change in BCVA from baseline to month 6 was +6.6 letters (95% confidence interval [CI], 4.9-8.3), and after institution of bimonthly treatment the mean change in BCVA at month 12 was +4.8 letters (95% CI, 2.9-6.7; P < 0.001) and +6.5 letters (95% CI, 4.2-8.8) at month 18. The proportion of participants gaining ≥10 and ≥15 letters was 24.8% and 13.8% at month 12 and 34.9% and 19.3% at month 18, respectively. Participants received a mean of 6.8 and 8.5 injections over 12 and 18 months, respectively. No new ocular or nonocular safety findings were observed during the study. CONCLUSIONS: The BCVA gain achieved in the initial 6-month treatment period was maintained with an additional 12 months of bimonthly ranibizumab PRN treatment.

Susac's syndrome: the value of fundus fluorescein angiography.

A 19-year-old woman presented with a 4-week history of headache, ataxia, vertigo, confusion, intermittent blurred vision in the right eye and intermittent hearing loss. MRI revealed white matter lesions and 'pepper pot' lesions of the corpus callosum. The cerebrospinal fluid had raised protein and lymphocytes. Fundal examination revealed multiple peripheral arterial occlusions in the both eyes confirmed with fundus fluorescein angiography (FFA). A diagnosis of Susac's syndrome was made. The patient was initially treated with steroids, followed by azathioprine and intravenous immunoglobulins (IVIg). Clinical improvement was noted, associated with improvement of the retinal circulation on FFA.

A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study.

Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%-1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, -1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated.

A case report of orbital haemorrhage associated with endoscopic sinus surgery and reversible sight loss: a multidisciplinary approach to management.

We report a case of intraoperative orbital haemorrhage as a complication of endoscopic sinus surgery performed under general anaesthesia. Initial unilateral complete visual loss occurred, but recovered due to accurate and early diagnosis combined with urgent surgical intervention. This patient's case is reported to illustrate the importance of early recognition of clinical signs and how a stepwise approach to management can result in a favourable visual outcome. Moreover, the mechanisms and pathophysiology of visual loss due to orbital haemorrhage following endoscopic sinus surgery are discussed.

Analysis of macular thickness in British population using optical coherence tomography (OCT): an emphasis on interocular symmetry.

PURPOSE: To evaluate macular thickness measurements in normal subjects from British origin, to assess interocular asymmetry using optical coherence tomography (OCT) and to establish standard values for macular and foveal thickness. METHODS: Two hundred eyes of 100 normal individuals underwent serial scans using fast macular thickness map protocol in the Stratus OCT version 3.51, with foveal fixation. Minimum foveal thickness (MFT), central 1 mm average foveal thickness (AFT), total foveal volume (TFV) and total macular volume (TMV at 6 mm) of both eyes were assessed. The interocular asymmetry was measured and statistically analyzed. RESULTS: The mean +/- SD (N = 200) was 173 +/- 23 microm for MFT and 203 +/- 24 microm for AFT. The mean difference +/- SD between the two eyes was (3.5 +/- 14.5 microm at p = 0.17) for MFT, (6.4 +/- 14.7 microm at p = 0.06) for AFT, (0.007 mm3 +/- 0.007 at p = 0.06) for TFV and (0.19 +/- 0.35 at p = 0.07) for TMV. CONCLUSION: Our study provides a normative database for macular thickness and volume parameters in normal British individuals using Stratus OCT. The MFT, AFT, TMV and TFV measurements were not statistically significant between the two eyes. Hence, the interocular symmetry should be considered on interpretation of macular thickness values especially in cases of uniocular or asymmetrical macular involvement.

The effect of phacoemulsification cataract surgery on the measurement of retinal nerve fiber layer thickness using optical coherence tomography.

PURPOSE: To evaluate whether the measurement of retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT) changes after cataract surgery. METHODS: This prospective, randomized, observational, cross-sectional clinical study included 24 eyes of 24 patients who underwent phacoemusification with implant. All patients had no preexisting retinal or optic nerve pathology or other media opacities that might influence the RNFL thickness. The classification and the grading of cataract were based on the Lens Opacities Classification System III (LOCS III). All eyes were scanned immediately before cataract surgery with OCT using Fast RNFL program. All eyes had circular scans around the optic disk with a diameter of 3.4 mm. The OCT was repeated 4 weeks after surgery when the patients returned for postoperative check using the same programme. RESULTS: The mean preoperative RNFL thickness was 84.9 +/- 16.5. The postoperative mean RNFL thickness was 93.0 +/- 17.6. The pre-and postoperative values of the mean RNFL and signal/noise ratio (SNR) are statistically significant (P < 0.05). CONCLUSIONS: Lens opacities may affect the image quality of OCT scans used to measure RNFL thickness as indicated by preoperative low SNR. Cataract extraction results in an apparent increase of the RNFL thickness.

Zonular dialysis and vitreous loss with a J-shaped hydrodissection cannula during phacoemulsification.

We report a complication that occurred during clear corneal phacoemulsification. When saline was injected during hydrodissection with a 27-gauge J-shaped cannula attached to a 2.0 mL luer-lock polypropylene syringe, the cannula dislodged and slipped behind the iris, hooking to the lens equator. Although the cannula was carefully removed, 3 clock hours of zonular dialysis were observed between the 4 o'clock and 7 o'clock meridians. After phacoemulsification, lens aspiration, and in-the-bag intraocular lens implantation, vitreous was noted inferiorly and the anterior vitrectomy was completed.