Retinal vascular calibre, geometry and progression of diabetic retinopathy in type 2 diabetes mellitus.

PURPOSE: To determine whether changes in retinal vascular calibre and geometry are associated with progression of diabetic retinopathy in type 2 diabetes (T2D). PROCEDURES: The retinal vascular calibre and geometry of 30 subjects with more than 20 years of diagnosed T2D with no retinopathy (NR) were compared to 30 subjects that progressed to proliferative diabetic retinopathy (PDR). The images of PDR subjects included in this study were those obtained before the onset of retinopathy. The diameter of retinal arterioles (CRAE), retinal venules (CRVE), tortuosity of retinal vessels, junctional exponent deviation (JE(a)) and fractal dimension (D(f)) were measured using Singapore I Vessel Assessment (SIVA 3.0) software and compared using Mann-Whitney U test. RESULTS: The median CRAE and the median CRVE were significantly wider in PDR subjects compared to NR subjects (p = 0.014 and 0.016), respectively. Curvature tortuosity of the retinal arteries and veins and D(f) were significantly decreased in the PDR subjects compared to NR subjects (p = 0.015, 0.016 and 0.03, respectively). The JE(a) was significantly increased in PDR subjects (p = 0.01). CONCLUSIONS: Retinal vessel calibre and geometry of the retinal vasculature may be important risk factors for the progression to PDR. More longitudinal prospective studies will be needed to further explore the findings of this study.

A review and update on the ophthalmic implications of Susac syndrome.

Susac syndrome is a rare condition presumed to be immune-mediated occlusion of small arterial vasculature principally of the brain, inner ear, and retina. Clinically, the syndrome manifests as a pathognomonic triad of encephalopathy, hearing loss, and branch retinal artery occlusion. Early recognition and diagnosis is important as delayed treatment may be profound and result in deafness, blindness, dementia, and other neurological deficits. The plethora of imaging technology, including magnetic resonance imaging, retinal fluorescein angiography, optical coherence tomography, and optical coherence tomography angiography, allows deeper and more discrete anatomical-physiological correlation of underlying pathology, early diagnosis, and imaging biomarkers for early detection of relapse during follow-up. We highlight the current clinical classification of Susac syndrome, available investigations, treatment, and care pathways.

New macular findings in individuals with biallelic KLHL7 gene mutation.

OBJECTIVE: The ubiquitin-proteasome system pathway has been recognised as a crucial cellular mechanism for the proper function of photoreceptor cells. In particular, ubiquitin ligases (E3s) recognise and ubiquitinate specific proteins for degradation. The KLHL7 protein (a BTB-Kelch protein) has been found to play an important role in this process. There have been several reports that heterozygous mutations in the KLHL7 gene in adults are responsible for a rare cause of late-onset autosomal dominant retinitis pigmentosa with preservation of central vision and homozygous mutations in two young children, with Crisponi syndrome (CS)/cold-induced sweating syndrome type 1, result in a recessive form of early-onset peripheral retinal dystrophy type changes. The majority of children do not survive through to adulthood. The objective of this study is to report the visual symptoms and signs of two young adults clinically diagnosed with overlapping BOS/Cisproni syndrome, expanding the phenotypic presentation of KLHL7 gene mutations. METHODS AND ANALYSIS: This is a case report of the ophthalmic findings of two siblings with biallelic KLHL7 gene mutations. Siblings born to a non-consanguineous family and diagnosed with the overlapping clinical phenotype of Bohring-Opitz and and confirmed biallelic KLHL 7 gene mutation by whole exome sequencing were identified. Ophthlamic history and fundal examination was performed and analysed. RESULTS: Both patients had similar retinal findings. The fundus shows confluent hypopigmented/pale yellow lesions in the mid-periphery. The optic disc appears to be pale with a ring of atrophy and vessels appear attenuated. The macular of the younger patient shows a depigmented area around the fovea giving a bull's-eye appearance while the older sibling shows a fibrotic ring around the fovea suggesting a more advanced pathology. CONCLUSION: This paper expands the retinal phenotype to include a distinctive maculopathy in a recently described homozygous mutation in the KLHL7 gene in two young adults presenting with features that overlap the Bohring-Opitz syndrome and CS.

Clinicopathologic Correlation of Lens Epithelial Metaplasia and Late Intraocular Lens Dislocation After Repair of Retinal Detachment.

IMPORTANCE: In-the-bag intraocular lens dislocation is an uncommon but serious complication of cataract surgery in patients with previous repair of retinal detachment. The causative mechanism is currently unknown. We report histologic findings from a retrospective case series from 1993 to 2010 and suggest a possible mechanism to explain this association. OBSERVATIONS: Clinical characteristics of 8 patients presenting with in-the-bag intraocular lens dislocation after repair of retinal detachment were evaluated. Explanted capsular bags from 3 of these patients were compared with pathologic changes of crystalline lenses associated with retinal detachment. Histologic examination of the explanted capsular bags revealed a paucicellular membrane that covered the concertina-like folded surface of the lens capsule. The lens capsule was devoid of epithelial cell nuclei and showed excessive thickening with the presence of spindle-shaped cells, such as fibroblasts. Collagen fibers were noted in the extracellular matrix. CONCLUSIONS AND RELEVANCE: Previous studies of crystalline lens pathologic findings associated with retinal detachment have shown changes in the epithelium with migration and subsequent metaplasia of epithelial cells, resulting in excessive thickening of the anterior capsule with a layer of fibrous tissue. In this retrospective series, similar histologic findings were seen, suggesting that zonular dehiscence and lens dislocation may result from progressive capsular contraction secondary to retinal detachment-induced lens epithelial metaplasia.

A prospective randomised controlled clinical trial comparing a combination of repeated intravitreal Ozurdex and macular laser therapy versus macular laser only in centre-involving diabetic macular oedema (OZLASE study).

BACKGROUND/AIMS: To evaluate the clinical efficacy and safety of combined repeated Ozurdex and macular laser therapy (MLT) compared with MLT monotherapy in participants with visual impairment due to centre-involving diabetic macular oedema (DMO). METHODS: 80 patients with best corrected visual acuity (BCVA) between 54 and 78 ETDRS letters due to centre-involving DMO were randomised to combination therapy with Ozurdex and MLT or MLT only. The combination arm received mandated Ozurdex injections at baseline and 16 weeks followed by retreatment criteria-guided pro-re-nata therapy at 32 and 48 weeks. Patients randomised to MLT only were treated every 16 weeks if clinically significant macular oedema was present. The primary outcome was the mean change from baseline in BCVA between arms at 56 weeks. RESULTS: The mean change in BCVA at 56 weeks was -0.3 (SD 11.4) ETDRS letters in the combination arm versus +0.4 (SD 9.6) ETDRS (Early Treatment Diabetic Retinopathy study) letters in the MLT arm (effect estimate 1.15 (95% CI -3.32 to 5.61)). However, at 56 weeks, a post hoc comparison of central subfield thickness (CST) showed a decrease of -113 µm (IQR -218, -64) (combination) versus -17 µm (-128, 12) (MLT arm) (p<0.001). Elevated intraocular pressure requiring topical therapy was observed in 8 (20%) eyes in the combination versus 1 (2.5%) in the MLT arm. 33% (9/27) of phakic patients in the combination arm underwent cataract surgery. CONCLUSIONS: Visual outcome following combination therapy did not differ from MLT alone in the centre-involving DMO despite a significant decrease in CST likely due to an entry visual acuity-related ceiling effect and cataract development. TRIAL REGISTRATION NUMBER: EudraCT 2011-003339-74.

Interobserver agreement in detecting spectral-domain optical coherence tomography features of diabetic macular edema.

PURPOSE: To evaluate interobserver agreement for the detection of spectral-domain optical coherence tomography (SDOCT) features of diabetic macular edema (DME). METHOD: Cross-sectional study in which 2 retinal specialists evaluated SDOCT scans from eyes receiving treatment for DME. Scans from 50 eyes with DME of 39 patients were graded for features of DME including intra-retinal fluid (IRF), diffuse retinal oedema (DRE), hyper-reflective foci (HRF), subretinal fluid (SRF), macular fluid and vitreomacular traction (VMT). Features were graded as present or absent at zones involving the fovea, 1mm from the fovea and the whole scan of 49 line scans. Analysis was performed using cross-tabulations for percentage concordance and kappa values (κ). RESULTS: In the 2950 line scans analysed, there was an increase in percentage concordance for DRE and HRF when moving from a foveal line scan, 1mm zone and then to a whole scan analysis (88% vs 94% vs 96%) and (88% vs 94% vs 94%) respectively with κ ranging from substantial to almost perfect. Percentage concordance for SRF was 96% at all 3 regions analysed, whilst IRF was 96% at fovea and 98% at higher number of line-scans analysed. Concordance for MF was 100% at fovea and 98% at 1mm zone and whole scan with almost perfect and substantial κ respectively. κ agreement was substantial for VMT at all regions analysed. CONCLUSION: We report a high level of interobserver agreement in the detection of SDOCT features of DME. This finding is important as detection of macular fluid is used to guide retreatment with anti-angiogenic agents.

Injection frequency and response to bevacizumab monotherapy for diabetic macular oedema (BOLT Report 5).

AIMS: To explore the parameters that influence injection frequency in patients treated with intravitreal bevacizumab (ivB) for diabetic macular oedema. Injection frequency was considered as a surrogate marker of persistent or recurrent oedema. METHODS: A post hoc analysis of the patients randomised to the ivB arm of a prospective, randomised controlled trial (A prospective randomized trial of intravitreal bevacizumab or laser therapy in the management of diabetic macular edema (BOLT study)) was done to assess the factors that may determine the injection frequency at 12 and 24 months. The injection response patterns were classified based on the specific time point at which the macula was first defined as 'dry'. RESULTS: Eyes with better baseline visual acuity less frequently had persistent oedema and had fewer recurrences in the second year. All eyes with baseline subretinal detachment showed persistent macular oedema at 24 months. None of the other factors assessed influenced injection frequency or response in the first or second year. CONCLUSIONS: Good long-term response is predicted by resolution of macular oedema by 4 months. However, approximately 20% of patients with persistent oedema at 12 months achieved a dry macula and 50% gained more than 15 letters at 24 months with sustained treatment, suggesting that oedema at 4 or 12 months should not be used as a stopping criterion for treatment.

Treatment of recurrent vulvo-vaginal candidiasis with sustained-released butoconazole pessary.

Vulvo-vaginal candidiasis (VVC) is a common infection among women. 5% of women with acute infection experience recurrent vulvo-vaginal candidiasis (RVVC). There is currently no optimal or recommended regime for RVVC. Although antifungal agents, such as imidazoles, have been successfully used as a first-line treatment for acute VVC, its effectiveness is limited in RVVC. This could be due to patient factors, drug application (such as leakage) or dosing factors. A sustained-release (SR) bioadhesive vaginal cream (2% butoconazole nitrate) has incorporated VagiSite technology, a topical drug delivery system that allows SR of the drug. We describe its efficacy and the successful use of a butoconazole-SR formulation in the treatment of two cases of RVVC.

Repeatability of Spectralis OCT measurements of macular thickness and volume in diabetic macular edema.

PURPOSE: We estimated coefficients of repeatability for Spectralis optical coherence tomography (OCT)-derived automated retinal thickness and volume measurements in subjects with center-involving diabetic macular edema (DME). METHODS: A total of 50 eyes of 50 consecutive patients with center-involving DME underwent four consecutive "fast" volume scans at a single session using one OCT device operated by one of two experienced operators. Bland-Altman coefficients of repeatability (CR) were calculated for automated retinal thickness measurements in the nine Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields, center point thickness, and total macular volume. Scans were evaluated for significant automated retinal boundary detection error and revised estimates for CR calculated with these scans excluded. RESULTS: CR in the central subfield was 8.03 µm (95% confidence interval [CI] 7.70-8.35 µm). In other subfields, CR ranged from 6.54 to 18.25 µm. Scan sets from 13 subjects had significant boundary detection error; reanalysis with these excluded yielded a CR for the central subfield of 7.44 µm with CR for all other subfields <8 µm. CONCLUSIONS: Retinal thickness measurements in subjects with DME obtained using Spectralis OCT are considerably less variable than has been reported with other devices. Changes in central subfield thickness >8 µm can be considered more indicative of true clinical change rather than measurement variability. This finding informs clinical practice and clinical trial design.