Quality-adjusted life years in macular oedema due to age-related macular degeneration, diabetes and central retinal vein occlusion: the impact of anti-VEGF agents in a tertiary centre in Greece.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), and macular oedema due to central retinal vein occlusion (CRVO) are leading causes of vision loss, currently managed with anti-vascular endothelial growth factor injections (anti-VEGF). The aim of this study was to calculate QALYs in patients with nAMD, DME, and CRVO treated with anti-VEGF agents (QALYs+) in a Greek tertiary hospital setting and compare them to theoretical QALYs that the patients would have without treatment (QALYs-). MATERIAL AND METHODS: The study included 143 treatment-naive patients with macular oedema due to nAMD (n = 79), DME (n = 57), and CRVO (n = 7), who received anti-VEGF injections as monotherapy according to the Treat-and-Extend (T&E) protocol. The anti-VEGF agents were ranibizumab and aflibercept in equivalent fractions. QALYs where calculated by the formula QALY = Utility Value × Time, where "Time" refers to the follow-up period of the study. For QALYs-, we assumed that visual acuity remained unchanged during this period. RESULTS: Mean follow-up time was 1.3 ± 1.2 years in the nAMD group, 1 ± 1.3 years in the DME group, and 0.5 ± 1 years in the CRVO group. There was no statistically significant difference between QALYs- and QALYs+ in all three ocular pathologies for the study period (p > 0.05 for each of the three statistical tests performed). DISCUSSION/CONCLUSION: Possible explanations for the lack of significant difference between QALYs - and QALYs + in nAMD, DME, and CRVO groups, may be the short time horizon used in this analysis, the inclusion of data from the better-seeing eye (BSE) and the specific socio-economic, geographical and health care characteristics of this rural Greek area.

Scleral buckling surgery for stage 4A and 4B retinopathy of prematurity in critically ill neonates.

PURPOSE: To determine the efficacy of scleral buckling in eyes with stage 4A and 4B retinopathy of prematurity (ROP). METHODS: Seven eyes of five premature infants underwent scleral buckling for stage 4 ROP in zone II. Five eyes had stage 4A ROP, and two eyes had stage 4B ROP. Six eyes had previous diode laser photocoagulation, and one eye had received an intravitreal ranibizumab injection. Scleral buckling was the procedure of choice due to lack of access to specialized pediatric vitrectomy instrumentation. Average age at surgery was 3.4 months. Postoperative anatomic retinal status, visual acuity outcome and refractive error were assessed. RESULTS: The scleral buckle was removed on average 8 months after surgery. Retinal reattachment was achieved in all seven eyes. At final follow-up one eye had macular ectopia and disc dragging, one eye had a macular traction fold and two eyes had optic disc pallor. Average myopic error after buckle removal was -7.5 D. CONCLUSION: Scleral buckling can be performed safely and effectively in 4A and 4B stage ROP in critically ill infants, when access to specialized pediatric vitrectomy instrumentation is limited. This surgical technique may provide adequate relief of vitreoretinal traction with improved visual potential.

CYP1A2 rs762551 and ADORA2A rs5760423 Polymorphisms in Patients with Blepharospasm.

Blepharospasm (BSP) is a neurological movement disorder. Coffee consumption has been found to have a protective effect against BSP. BSP and apraxia of eyelid opening are particularly common among patients with PD. The CYP1A2 rs762551 and ADORA2A rs5760423 variants have been previously marginally associated with the risk of PD and are also implicated in caffeine metabolism pathways. The aim of the present study was to evaluate the effect of the CYP1A2 rs762551 and ADORA2A rs5760423 variants on BSP. A Southeastern European Caucasian (SEC) cohort of 206 BSP patients and 206 healthy controls was genotyped for rs762551 and rs5760423. CYP1A2 rs762551 was associated with a decreased BSP risk in the dominant (OR (95% CI) 0.62 (0.41-0.92), p = 0.017), log-additive (OR (95% CI) 0.68 (0.51-0.92), p = 0.011), and co-dominant modes (for the CC genotype OR (95% CI) 0.49 (0.25-0.93), p = 0.038). We provide preliminary evidence that CYP1A2 rs762551 is associated with BSP. Further studies and replication of our results are needed.

FLT1 genetic variation predisposes to neovascular AMD in ethnically diverse populations and alters systemic FLT1 expression.

PURPOSE: Current understanding of the genetic risk factors for age-related macular degeneration (AMD) is not sufficiently predictive of the clinical course. The VEGF pathway is a key therapeutic target for treatment of neovascular AMD; however, risk attributable to genetic variation within pathway genes is unclear. We sought to identify single nucleotide polymorphisms (SNPs) associated with AMD within the VEGF pathway. METHODS: Using a tagSNP, direct sequencing and meta-analysis approach within four ethnically diverse cohorts, we identified genetic risk present in FLT1, though not within other VEGF pathway genes KDR, VEGFA, or VASH1. We used ChIP and ELISA in functional analysis. RESULTS: The FLT1 SNPs rs9943922, rs9508034, rs2281827, rs7324510, and rs9513115 were significantly associated with increased risk of neovascular AMD. Each association was more significant after meta-analysis than in any one of the four cohorts. All associations were novel, within noncoding regions of FLT1 that do not tag for coding variants in linkage disequilibrium. Analysis of soluble FLT1 demonstrated higher expression in unaffected individuals homozygous for the FLT1 risk alleles rs9943922 (P = 0.0086) and rs7324510 (P = 0.0057). In silico analysis suggests that these variants change predicted splice sites and RNA secondary structure, and have been identified in other neovascular pathologies. These data were supported further by murine chromatin immunoprecipitation demonstrating that FLT1 is a target of Nr2e3, a nuclear receptor gene implicated in regulating an AMD pathway. CONCLUSIONS: Although exact variant functions are not known, these data demonstrate relevancy across ethnically diverse genetic backgrounds within our study and, therefore, hold potential for global efficacy.

Ocular rigidity, outflow facility, ocular pulse amplitude, and pulsatile ocular blood flow in open-angle glaucoma: a manometric study.

PURPOSE: To compare ocular rigidity (OR) and outflow facility (C) coefficients in medically treated open-angle glaucoma (OAG) patients and controls, and to investigate differences in ocular pulse amplitude (OPA) and pulsatile ocular blood flow (POBF) between the two groups. METHODS: Twenty-one OAG patients and 21 controls undergoing cataract surgery were enrolled. Patients with early or moderate primary or pseudoexfoliative OAG participated in the glaucoma group. A computer-controlled system, consisting of a pressure transducer and a microstepping device was employed intraoperatively. After cannulation of the anterior chamber, IOP was increased by infusing the eye with microvolumes of saline solution. IOP was recorded after each infusion step. At an IOP of 40 mm Hg, an IOP decay curve was recorded for 4 minutes. OR coefficients, C, OPA, and POBF were estimated from IOP and volume recordings. RESULTS: There were no differences in age or axial length in the two groups. The OR coefficient was 0.0220 ± 0.0053 µl(-1) in the OAG and 0.0222 ± 0.0039 µl(-1) in the control group (P = 0.868). C was 0.092 ± 0.082 µL/min/mm Hg in the glaucoma group compared with 0.149 ± 0.085 µL/min/mm Hg in the control group at an IOP of 35 mm Hg (P < 0.001) and 0.178 ± 0.133 µL/min/mm Hg vs. 0.292 ± 0.166 µL/min/mm Hg, respectively, at an IOP of 25 mm Hg (P < 0.001). There were no differences in OPA or POBF between the two groups in baseline and increased levels of IOP (P > 0.05). CONCLUSIONS: Manometric data reveal lower C in OAG patients and increased C with increasing IOP. There were no differences in the OR coefficient, OPA, and POBF between medically treated OAG patients and controls, failing to provide evidence of altered scleral distensibility and choroidal blood flow in OAG.

Transscleral diode laser cyclophotocoagulation for refractory glaucoma secondary to juvenile idiopathic arthritis: a short term follow-up.

To evaluate the success rates of transscleral diode cyclophotocoagulation (TD-CPC) for refractory secondary glaucoma in a paediatric patient with juvenile idiopathic arthritis. Report of a case of a 6-year-old boy suffering from severe uveitis, and secondary open angle glaucoma. The patient had undergone bilateral cataract surgery, two prior trabeculectomies in the left and one in the right eye. He was under systemic immunomodulation with methotrexate and cyclosporine. He presented with medically uncontrolled glaucoma, with an intraocular pressure (IOP) of 36 and 34 mmHg in the right and left eye, respectively, under maximal medical antiglaucoma therapy. TD-CPC was performed under general anesthesia, including a total of 20 spots in the right and 34 in the left eye (2,000 mW, 2 s/spot) applied in one session. Visual acuity remained stable in the right eye and deteriorated in the left eye from 0.1 to no light perception. Postoperative hypotony was present 1 month post op and IOP was 14 mmHg in the left and 17 mmHg in the right eye, respectively, in the 6-month follow-up with a topical beta-blocker. The anterior chamber was quiet in both eyes. TD-CPC was effective in the short term as IOP lowering therapy in a pediatric patient with refractory uveitic glaucoma.

Systems biology-based analysis implicates a novel role for vitamin D metabolism in the pathogenesis of age-related macular degeneration.

Vitamin D has been shown to have anti-angiogenic properties and to play a protective role in several types of cancer, including breast, prostate and cutaneous melanoma. Similarly, vitamin D levels have been shown to be protective for risk of a number of conditions, including cardiovascular disease and chronic kidney disease, as well as numerous autoimmune disorders such as multiple sclerosis, inflammatory bowel diseases and type 1 diabetes mellitus. A study performed by Parekh et al. was the first to suggest a role for vitamin D in age-related macular degeneration (AMD) and showed a correlation between reduced serum vitamin D levels and risk for early AMD. Based on this study and the protective role of vitamin D in diseases with similar pathophysiology to AMD, we examined the role of vitamin D in a family-based cohort of 481 sibling pairs. Using extremely phenotypically discordant sibling pairs, initially we evaluated the association of neovascular AMD and vitamin D/sunlight-related epidemiological factors. After controlling for established AMD risk factors, including polymorphisms of the genes encoding complement factor H (CFH) and age-related maculopathy susceptibility 2/HtrA serine peptidase (ARMS2/HTRA1), and smoking history, we found that ultraviolet irradiance was protective for the development of neovascular AMD (p = 0.001). Although evaluation of serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) was higher in unaffected individuals than in their affected siblings, this finding did not reach statistical significance. Based on the relationship between ultraviolet irradiance and vitamin D production, we employed a candidate gene approach for evaluating common variation in key vitamin D pathway genes (the genes encoding the vitamin D receptor [VDR]; cytochrome P450, family 27, subfamily B, polypeptide 1 [CYP27B1]; cytochrome P450, family 24, subfamily A, polypeptide 1 [CYP24A1]; and CYP27A1) in this same family-based cohort. Initial findings were then validated and replicated in the extended family cohort, an unrelated case-control cohort from central Greece and a prospective nested case-control population from the Nurse's Health Study and Health Professionals Follow-Up Studies, which included patients with all subtypes of AMD for a total of 2,528 individuals. Single point variants in CYP24A1 (the gene encoding the catabolising enzyme of the vitamin D pathway) were demonstrated to influence AMD risk after controlling for smoking history, sex and age in all populations, both separately and, more importantly, in a meta-analysis. This is the first report demonstrating a genetic association between vitamin D metabolism and AMD risk. These findings were also supplemented with expression data from human donor eyes and human retinal cell lines. These data not only extend previous biological studies in the AMD field, but further emphasise common antecedents between several disorders with an inflammatory/immunogenic component such as cardiovascular disease, cancer and AMD.

Plasma and aqueous humour levels of ghrelin in open-angle glaucoma patients.

BACKGROUND: To compare aqueous humour and plasma levels of ghrelin, a peptide recently identified in human eyes, in patients with open-angle glaucoma and controls. DESIGN: Cross-sectional, controlled, hospital-based study. PARTICIPANTS: Twenty-four open-angle glaucoma (17 primary open-angle and 7 pseudo-exfoliation glaucoma) patients and 30 controls were included. All participants were patients scheduled for cataract or glaucoma surgery. Patients with other ocular pathology, previous ocular surgery or diabetes were excluded. METHODS: Blood samples were collected before elective surgery. Aqueous humour was aspirated from the anterior chamber through a paracentesis with a 27-G needle under sterile conditions before any tissue manipulation. Ghrelin quantification was performed with commercially available Radioimmunoassay kits. MAIN OUTCOME MEASURE: Ghrelin levels in aqueous humour and plasma. RESULTS: Plasma levels of ghrelin were 490.5 ± 156.0 pg/mL in the open-angle glaucoma and 482.2 ± 125.4 pg/mL in the control group (Mann-Whitney test, P = 0.897). Aqueous humour levels of ghrelin were 85.5 ± 15.4 and 123.4 ± 25.5 pg/mL in the respective groups (P < 0.001). The ratio of plasma/aqueous humour ghrelin concentration was higher in the open-angle glaucoma versus the control group (5.75 ± 1.92 vs. 4.00 ± 1.04, P < 0.001). There was no difference in aqueous humour levels of ghrelin between primary open-angle glaucoma and pseudo-exfoliation glaucoma patients (P = 0.494). CONCLUSIONS: Aqueous humour levels of ghrelin were significantly lower in open-angle glaucoma patients, compared with controls. This difference may manifest a role of ghrelin in the disease process or a consequence of antiglaucoma treatment.

Detection of macular photocoagulation scars with confocal infrared reflection imaging.

BACKGROUND AND OBJECTIVE: To study the diagnostic reliability (specificity and sensitivity) of confocal infrared reflection in detecting threshold argon laser photocoagulation scars in the macula. PATIENTS AND METHODS: Fifty-six maculae with diabetic macular edema were evaluated by biomicroscopic slit-lamp fundus examination, digital color fundus photography, digital fundus fluorescein angiography, and digital infrared reflection images. Three examiners evaluated whether the eye had undergone any laser photopexy in the macula. RESULTS: Sensitivity, specificity, and false-positive and false-negative results were calculated for each method. Fluorescein fundus angiography and infrared imaging, although using different approaches, both detect pigment epithelium changes such as laser scars. It seems that both methods are of equal specificity. On the other hand, both biomicroscopic fundus examination and digital color photography showed poor reliability. CONCLUSION: Infrared reflection imaging is an easy, noninvasive method with excellent sensitivity and specificity in detecting photocoagulation scars from previous threshold laser treatment. It may be useful in estimating photocoagulated areas, especially if threshold treatment has been applied.

Resolution of macular edema in idiopathic juxtafoveal telangiectasis using PDT.

A 57-year-old woman was treated by photodynamic therapy for macular edema due to idiopathic juxtafoveal telangiectasis (presumed type 1A) without subretinal neovascularization. Initial visual acuity of the treated eye was 20/200 and it improved to 20/40 by 3 months after the photodynamic therapy session. Visual acuity remained stable 32 months after the treatment. Color photographs and fundus fluorescein angiography before and after photodynamic therapy revealed regression of hemorrhages, exudates, and fluorescein leakage. Photodynamic therapy has long-term benefits for the patient with idiopathic juxtafoveal telangiectasis, presumed type 1A, because it can improve visual acuity and macular edema.