Risk of retinal vein occlusion following COVID-19 vaccination: a self-controlled case series.

BACKGROUND: To evaluate the association between COVID-19 vaccination and retinal vein occlusion (RVO). METHODS: This multicentre self-controlled case series included patients with RVO seen in five tertiary referral centres in Italy. All adults who received at least one dose of the BNT162b2, ChAdOx1 nCoV-19, mRNA-1273 or Ad26.COV2.S vaccine and had a first diagnosis of RVO between January 01, 2021, and December 31, 2021 were included. Incidence rate ratios (IRRs) of RVO were estimated using Poisson regression, comparing rates of events in a 28-day period following each dose of vaccination and in the unexposed control periods. RESULTS: 210 patients were included in the study. No increased risk of RVO was observed after the first dose (1-14 days IRR: 0.87, 95% CI: 0.41-1.85; 15-28 days IRR: 1.01, 95% CI: 0.50-2.04; 1-28 days IRR: 0.94, 95% CI: 0.55-1.58) and second dose of vaccination (1-14 days IRR: 1.21, 95% CI: 0.62-2.37; 15-28 days IRR: 1.08, 95% CI: 0.53-2.20; 1-28 days IRR: 1.16, 95% CI: 0.70-1.90). No association between RVO and vaccination was found in subgroup analyses by type of vaccine, gender and age. CONCLUSIONS: This self-controlled case series found no evidence of an association between RVO and COVID-19 vaccination.

Outcomes of Conventional 8.0-mm Versus Large 9.0-mm Diameter Deep Anterior Lamellar Keratoplasty for Keratoconus.

PURPOSE: The purpose of the study was to compare the clinical outcomes of large 9.0-mm diameter and conventional 8.0-mm big-bubble deep anterior lamellar keratoplasty (DALK). METHODS: In this comparative, retrospective interventional case series, medical records of 124 cases of large 9.0-mm diameter DALK from January 2017 to December 2019 and 133 conventional 8.0-mm DALK from January 2014 to December 2016 performed by a single surgeon for the indication of keratoconus were reviewed. Main outcome measures were best spectacle-corrected visual acuity (BSCVA), refractive astigmatism (RA), and postoperative complication rates. RESULTS: Postoperative logarithm of the minimum angle of resolution BSCVA did not significantly differ between 9.0-mm and 8.0-mm DALK at any time points. Although the cumulative percentage of eyes achieving Snellen BSCVA of 20/40 or better was comparable between groups (9.0-mm DALK: 93%, 8.0-mm DALK: 90%, P = 0.571), the cumulative percentage of eyes achieving 20/20 or better (9.0-mm DALK: 44%, 8.0-mm DALK: 26%, P = 0.01) and 20/25 or better (9.0-mm DALK: 74%, 8.0-mm DALK: 59%, P = 0.03) was significantly higher in the 9.0-mm DALK group. RA was significantly lower in the 9.0-mm DALK group compared with the 8.0-mm DALK group during all time points ( P < 0.001). The percentage of eyes with RA less than or equal to 4.0 D was significantly lower in the 9.0-mm DALK patients (90%) compared with in 8.0-mm DALK group (72%) ( P = 0.002). Postoperative complication rates were similar between groups. CONCLUSIONS: Compared with conventional 8.0-mm DALK, large 9.0-mm DALK can provide superior visual outcomes at higher levels of Snellen BSCVA and significantly lower degrees of astigmatism without an increased risk of immune rejection and graft failure.

Effects of Serial Sessions of Activa Mask for the Treatment of Meibomian Gland Dysfunction.

INTRODUCTION: To analyze outcomes on objective ocular surface parameters and subjective symptoms of serial weekly sessions using the Activa mask in patients with meibomian gland dysfunction (MGD). METHODS: This is a prospective study including patients with symptomatic MGD who were treated with four weekly sessions using the Activa mask (SBM Sistemi, Turin, Italy). Noninvasive ocular surface examination was carried out before (T0) and 2 weeks after the last mask session (T1) using Idra (SBM Sistemi, Turin, Italy) for the measurement of: (1) noninvasive break-up time (NIBUT); (2) lipid layer thickness (LLT); (3) tear meniscus height (TMH); (4) meibomian gland loss (MGL) of upper and lower eyelids. The I-Pen tear osmolarity system (I-Med Pharma Inc, Dollard-des Ormeaux, Quebec, Canada) was used to measure tear osmolarity values. Ocular discomfort symptoms were ascertained by means of the ocular surface disease index (OSDI) questionnaire. RESULTS: All 25 patients (11 males, 14 females; mean age 57.1 ± 11.9 years) regularly completed the cycle of four mask sessions. No patients used prohibited medications, and no device-related adverse events were noted. At T1, mean values of NIBUT and LLT increased significantly compared to T0 (respectively from 6.0 ± 1.4 to 6.6 ± 1.2 s, P = 0.043, and from 53.2 ± 17.4 to 65.3 ± 16.3 nm, P < 0.001), while mean values of MGL and tear osmolarity decreased significantly (respectively from 17.1 ± 9.3 to 15.1 ± 8.0%, P = 0.014, and from 307.3 ± 12.2 to 301.5 ± 6.8 mOsm/l, P = 0.005). In parallel, OSDI score reduced significantly from 62.4 ± 11.7 at T0 to 34.5 ± 11.2 at T1 (P < 0.001). CONCLUSION: Weekly serial sessions using the Activa mask significantly improved objective parameters of the ocular surface as well as subjective ocular discomfort symptoms in patients with recalcitrant MGD. As a further benefit from the treatment, patients were able to avoid the use of concomitant medications, apart from tear substitutes, throughout the study.

10-year experience with lamellar keratoplasty for the surgical Management of Paediatric Corneal Diseases.

PURPOSE: To evaluate the outcomes of various lamellar keratoplasty techniques performed at our Institution in children aged 14 years or younger over the last decade. METHODS: This single-centre study reviewed 72 eyes that underwent lamellar keratoplasty for various indications. Deep anterior lamellar keratoplasty (DALK) was performed in 19 eyes, mushroom penetrating keratoplasty (PK) in 27 eyes and Descemet stripping automated endothelial keratoplasty (DSAEK) in 25 eyes. The main outcome measures included best spectacle-corrected visual acuity (BSCVA), complications and rate of graft failure which was defined as any graft requiring repeat transplantation. RESULTS: Best spectacle-corrected visual acuity (BSCVA) significantly improved after DALK, mushroom PK and DSAEK (all p < 0.05), with 50%, 60% and 56% of eyes reaching ≥20/40, respectively. Stromal rejection was observed in 1 eye (5.3%) after DALK, whilst endothelial rejection occurred in 1 eye after mushroom PK (3.7%) and 1 eye after DSAEK (4.0%). Overall survival was 100% after DALK (mean follow-up: 23.0 months), 92.8% after mushroom PK (mean follow-up: 42.3 months) and 96.0% after DSAEK (mean follow-up: 33.6 months). CONCLUSION: Deep anterior lamellar keratoplasty (DALK), mushroom PK and DSAEK offer good visual outcomes for children with corneal pathology, with low rates of immunological rejection and graft failure.

Accuracy of intraocular lens power calculation for cataract surgery after deep anterior lamellar keratoplasty.

BACKGROUND: The purpose of this study was to assess the accuracy of intraocular lens power (IOL) formulas for cataract surgery after deep anterior lamellar keratoplasty (DALK). METHODS: This retrospective study included eyes which had previously undergone DALK and underwent standard phacoemulsification with monofocal IOL implantation between January 2012 and January 2021 at Ospedali Privati Forlì "Villa Igea" (Forlì, Italy). The predicted spherical equivalent (SE) was calculated using the Barrett Universal II, Emmetropia Verifying Optical (EVO), Haigis, Hoffer Q, Hoffer QST, Holladay 1, Holladay II, Kane and SRK/T formulas. Prediction error (PE) was calculated as the actual postoperative SE refraction minus the SE predicted refraction. RESULTS: Eighty-two eyes of 82 patients were included. The mean PE was negative using all formulas. Friedman test revealed a statistically significant difference of the median absolute PE (MedAE) among the different IOL formulas (P = 0.005). On the basis of the MedAE, the formulas were ranked as follows: SRK/T (0.805 D), Kane (0.810 D), EVO (0.845 D), Hoffer QST (0.847 D), Barrett (0.895 D), Holladay 1 (0.915 D), Haigis (1.010 D) and Hoffer Q (1.070 D) formulas. CONCLUSIONS: All formulas had a tendency towards a myopic refractive shift in post-DALK eyes. Although the SRK/T, Kane, EVO and Hoffer QST formulas were more accurate, predictability of refractive outcomes was lower than in virgin eyes.

Impact of methylenetetrahydrofolate reductase C677T polymorphism on the efficacy of photodynamic therapy in patients with neovascular age-related macular degeneration.

The most severe visual impairments due to age-related macular degeneration (AMD) are frequently caused by the occurrence of choroidal neovascularization (CNV). Although photodynamic therapy with verteporfin (PDT-V) is currently a second-line treatment for neovascular AMD, it can be conveniently combined with drugs acting against vascular endothelial growth factor (anti-VEGF) to reduce the healthcare burden associated with the growing necessity of anti-VEGF intravitreal re-injection. Because the common 677 C > T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR-C677T; rs1801133) has been described as predictor of satisfactory short-term responsiveness of AMD-related CNV to PDT-V, we retrospectively examined the outcomes of 371 Caucasian patients treated with standardized, pro-re-nata, photodynamic regimen for 24 months. Responder (R) and non-responder (NR) patients were distinguished on the basis of the total number of scheduled PDT-V (TN-PDT-V) and change of best-corrected visual acuity (∆-BCVA). The risk for both TN-PDT-V and ∆-BCVA to pass from R to NR group was strongly correlated with CT and TT genotypes of MTHFR-C677T variant resulting, respectively, in odd ratios of 0.19 [95% CI, 0.12-0.32] and 0.09 [95% CI, 0.04-0.21] (P < 0.001), and odd ratios of 0.24 [95% CI, 0.15-0.39] and 0.03 [95% CI, 0.01-0.11] (P < 0.001). These pharmacogenetic findings indicate a rational basis to optimize the future clinical application of PDT-V during the combined treatments of AMD-related CNV, highlighting the role of thrombophilia to be aware of the efficacy profile of photodynamic therapy.

Clinical Outcomes of Preloaded Descemet Membrane Endothelial Keratoplasty Grafts With Endothelium Tri-Folded Inwards.

PURPOSE: To evaluate the initial outcomes and complications of Descemet membrane endothelial keratoplasty (DMEK) using donor tissues tri-folded with the endothelium inwards, preloaded at the Eye Bank, and delivered with bimanual pull-through technique. DESIGN: Prospective, noncomparative, interventional case series. METHODS: Setting: Eye bank and tertiary care eye department. PATIENT POPULATION: Forty-six consecutive eyes of 41 patients with Fuchs endothelial dystrophy with or without cataract operated between November 2016 and March 2017. INTERVENTION: DMEK tissues prepared with SCUBA technique and punched to a diameter of 8.25 mm were preloaded with the endothelium tri-folded inwards in an intraocular lens (IOL) cartridge with a 2.2-mm opening filled with the same tissue culture medium contained in the vial used for shipment to the surgeon. Standardized DMEK was performed as a single procedure (n = 15) or in combination with phacoemulsification and IOL implantation (n = 31) within 48 hours from preparation using a bimanual pull-through technique. MAIN OUTCOME MEASURES: Preparation and surgical times, intraoperative and postoperative complications, best spectacle-corrected visual acuity (BSCVA), endothelial cell density (ECD), and graft detachment rate. RESULTS: Preparation time averaged 26.2 ± 4.1 minutes (range 17-36 minutes), while the surgical time from opening of the stoppers to air fill of the anterior chamber never exceeded 9 minutes (range 3-9 minutes). Surgery was uneventful in all cases. Postoperative complications included graft detachment in 9 of 46 cases (19.6%), successfully managed in all cases by single rebubbling within 6 days from surgery, and glaucoma irresponsive to conservative treatment in 1 of 46 cases (2.1%). In all eyes without comorbidities (35 of 40 eyes) BSCVA was 20/25 (0.097 logMAR) or better as early as 3 months after surgery. Six months postoperatively, ECD was available in 24 of 25 eyes with an endothelial cell loss calculated as a percentage of the preoperative value determined at the eye bank (ranging from 2500 to 2800 cells/mm2) of 29.5% ± 14.8% (range 8.3%-52.1%). CONCLUSIONS: Delivering a preloaded DMEK tissue, tri-folded with the endothelium inwards, minimizes surgical time and costs without negatively affecting the outcomes of the procedure.

Effect of Factor XIII-A G185T Polymorphism on Visual Prognosis after Photodynamic Therapy for Neovascular Macular Degeneration.

Macular degenerations represent leading causes of central blindness or low vision in developed countries. Most of these severe visual disabilities are due to age-related macular degeneration (AMD) and pathologic myopia (PM), both of which are frequently complicated by subfoveal choroidal neovascularization (CNV). Photodynamic therapy with verteporfin (PDT-V) is still employed for CNV treatment in selected cases or in combined regimen. In Caucasian patients, the common polymorphism G185T of factor XIII-A gene (FXIII-A-G185T; rs5985) has been described as predictor of poor angiographic CNV responsiveness to PDT-V. Nevertheless, the prognostic implications of this pharmacogenetic determinant on long-term visual outcome after a PDT-V regimen have not been evaluated. We retrospectively selected Caucasian patients presenting with treatment-naive CNV and receiving standardized PDT-V protocol for two years. The study population included patients affected by subfoveal CNV secondary to AMD or PM. We assessed the correlations between the polymorphic allele T of FXIII-A-G185T and: (1) total number of photodynamic treatments; and (2) change in visual acuity from baseline to the end of the follow-up period. Considering a total study population of 412 patients with neovascular AMD or PM, the carriers of 185 T-allele of FXIII-A (GT or TT genotype) received a higher number of photodynamic treatments than patients without it (GG wild-type genotype) (p < 0.01; mean number of PDT-V: 5.51 vs. 3.76, respectively). Moreover, patients with 185 T-allele of FXIII-A had a more marked worsening of visual acuity at 24 months than those with the GG-185 wild genotype (p < 0.01; mean difference in logMAR visual acuity: 0.22 vs. 0.08, respectively). The present findings show that the G185T polymorphism of the FXIII-A gene is associated with significant differences in the long-term therapeutic outcomes of patients treated with standardized PDT-V protocol. The comprehensive appraisal of both anti-thrombophilic effects due to FXIII-A G185T variant and photo-thrombotic action of PDT-V toward CNV provides several clues about the rationale of this intriguing pharmacogenetic correlation. Further investigations are warranted to outline the appropriate paradigm for guiding PDT-V utilization in the course of the combined therapeutic protocol for neovascular macular degeneration.

Mechanism of inflammation in age-related macular degeneration: an up-to-date on genetic landmarks.

Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment among people over 50 years of age, accounting for up to 50% of all cases of legal blindness in Western countries. Although the aging represents the main determinant of AMD, it must be considered a multifaceted disease caused by interactions among environmental risk factors and genetic backgrounds. Mounting evidence and/or arguments document the crucial role of inflammation and immune-mediated processes in the pathogenesis of AMD. Proinflammatory effects secondary to chronic inflammation (e.g., alternative complement activation) and heterogeneous types of oxidative stress (e.g., impaired cholesterol homeostasis) can result in degenerative damages at the level of crucial macular structures, that is photoreceptors, retinal pigment epithelium, and Bruch's membrane. In the most recent years, the association of AMD with genes, directly or indirectly, involved in immunoinflammatory pathways is increasingly becoming an essential core for AMD knowledge. Starting from the key basic-research notions detectable at the root of AMD pathogenesis, the present up-to-date paper reviews the best-known and/or the most attractive genetic findings linked to the mechanisms of inflammation of this complex disease.

Mechanism of inflammation in age-related macular degeneration.

Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

Genetic predictors of response to photodynamictherapy.

In Western countries, therapeutic management of patients affected by choroidal neovascularization (CNV) secondary to different typologies of macular degeneration represents a major health care problem. Age-related macular degeneration is the disease most frequently associated with CNV development. Schematically, CNVs can be distinguished into classic and occult subtypes, which are characterized by variable natural history and different responsiveness to some therapeutic procedures. At present, the dramatic vision loss due to CNV can be mainly treated by two interventional strategies, which are utilizable in either single or combined modalities: photodynamic therapy with verteporfin (PDT-V), and intravitreal administration of drugs acting against vascular endothelial growth factor. The combined use of PDT-V and anti-angiogenic drugs represents one of the most promising strategies against neovascular macular degeneration, but it unavoidably results in an expensive increase in health resource utilization. However, the positive data from several studies serve as a basis for reconsidering the role of PDT-V, which has undergone a renaissance prompted by the need for a more rational therapeutic approach toward CNV. New pharmacogenetic knowledge of PDT-V points to exploratory prospects to optimize the clinical application of this intriguing photothrombotic procedure. In fact, a Medline search provides data regarding the role of several single nucleotide polymorphisms (SNPs) as genetic predictors of CNV responsiveness to PDT-V. Specifically, correlations between SNPs and different levels of PDT-V efficacy have been detected by examining the gene variants influencing (i) thrombo-coagulative pathways, i.e. methylenetetrahydrofolate reductase (MTHFR) 677C>T (rs1801133), factor V (F5) 1691G>A (rs6025), prothrombin (F2) 20210G>A (rs1799963), and factor XIII-A (F13A1) 185G>T (rs5985); (ii) complement activation and/or inflammatory processes, i.e. complement factor H (CFH) 1277T>C (rs1061170), high-temperature requirement factor A1 (HTRA1) promoter -512G>A (rs11200638), and two variants of the C-reactive protein (CRP) gene (rs2808635 and rs876538); and (iii) production and bioavailability of vascular endothelial growth factor (VEGFA -2578C>A [rs699947] and rs2146323). This article critically evaluates both the clinical plausibility and the opportunity to utilize the most important SNP-response interactions of PDT-V for an effective upgrade of the current anti-CNV therapeutic scenario. In addition, the pharmacogenetics of a very severe post-PDT-V adverse event, i.e. a decrease in acute vision, is briefly discussed. A comprehensive appraisal of the findings reviewed in this article should be carefully considered to design future trials aimed at verifying (after proper genotypic stratification of the enrolled patients) whether these innovative pharmacogenetic approaches will be able to improve the multifaceted interventional management of neovascular macular degeneration.

Impact of coagulation-balance gene predictors on efficacy of photodynamic therapy for choroidal neovascularization in pathologic myopia.

PURPOSE: To investigate whether different coagulation-balance genetic backgrounds might explain the variable clinical outcomes detected, after a single photodynamic therapy with verteporfin (PDT-V), in Caucasian patients with subfoveal choroidal neovascularization (CNV) secondary to pathologic myopia (PM). DESIGN: Retrospective, consecutive, nonrandomized, interventional cases series. PARTICIPANTS: Two hundred thirty-four patients exclusively treated with standardized PDT-V for the presence of PM-related classic CNV. METHODS: The enrolled patients were subdivided as responders or nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Three common gene polymorphisms, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, and methionine synthase reductase A66G, were genotyped by polymerase chain reaction in each patient. MAIN OUTCOME MEASURES: The measures of CNV responsiveness to PDT-V were the changes, respect to baseline, of fluorescein angiography CNV leakage, greatest linear dimension, and area of the lesion. Logistic regression analyses were performed to explore the predictive role of phenotypic (patient's age, baseline visual acuity, and baseline CNV area) and genotypic (all the mentioned mutations) variables regarding PDT-V efficacy. RESULTS: Responders to PDT-V were overrepresented within carriers of methylenetetrahydrofolate reductase 677 T-allele (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.8-5.4; P = 0.001) and, to a minor extent, among patients with better visual acuity at baseline (OR, 11.8; 95% CI, 1.6-88.0; P = 0.02). However, predictors of PDT-V lack of efficacy were patient's age (OR, 0.73; 95% CI, 0.62-0.86; P = 0.01) and, especially, factor XIII-A 185 GT/TT genotypes (OR, 0.19; 95% CI, 0.11-0.35; P = 0.0001). All the other considered predictive factors did not significantly influence the CNV responsiveness to PDT-V. CONCLUSIONS: These findings document the presence of pharmacogenetic correlations between common coagulation-balance gene polymorphisms and different CNV responsiveness to PDT-V in Caucasian patients with neovascular PM.

Parnaparin versus aspirin in the treatment of retinal vein occlusion. A randomized, double blind, controlled study.

INTRODUCTION: Retinal vein occlusion (RVO) is a common cause of unilateral visual loss. Evidence based treatment recommendations for patients with RVO cannot be made because of the lack of adequate clinical trials. To compare the efficacy and safety of aspirin and of a low molecular weight heparin, parnaparin, in the treatment of RVO. MATERIALS AND METHODS: In a multicenter, randomized, double blind, controlled trial eligible patients with a delay between symptoms onset and objective diagnosis of less than 15 days were randomized to aspirin 100 mg/day for 3 months or to a fixed daily dose of parnaparin, 12.800 IU for 7 days followed by 6.400 IU for a total of 3 months. Primary end-point of the study was the incidence of functional worsening of the eye with RVO at 6 months, as assessed by fluorescein angiography, visual acuity, and visual field. Study end-points were adjudicated by an independent committee. RESULTS: Sixty-seven patients were enrolled in the study and 58 of them (28 treated with parnaparin, 30 with aspirin) were evaluable for the analysis. Baseline characteristics were well balanced between groups. Functional worsening was adjudicated in 20.7% of patients treated with parnaparin and in 59.4% of patients treated with ASA (p=0.002). Recurrent RVO was diagnosed in 3 patients, all treated with ASA (p=n.s.). Bleeding rates were similar between the two groups. CONCLUSIONS: Parnaparin appears to be more effective than aspirin in preventing functional worsening in patients with RVO. The results of this study need to be confirmed in a larger clinical trial.

Coagulation gene predictors of photodynamic therapy for occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidence of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided into responders and nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms (i.e., factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G) were genotyped in each patient. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS: Regression models documented that PDT-V nonresponders were more frequently patients with the hyperfibrinolytic G185T mutation of factor XIII-A (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative of an overrepresentation of PDT-V responders among the combined carriers of thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% CI: 0.94-15.6; P = 0.07). All the other predictors considered did not significantly influence the short-term CNV responsiveness to PDT-V. CONCLUSIONS: These data provide evidence of the presence of a pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in patients with AMD with occult CNV.

12-month retrospective study and review of photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in age-related macular degeneration.

PURPOSE: To evaluate the 12-month visual outcome of photodynamic therapy with verteporfin (PDT-V) for patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration and to verify the predictive role of visual and angiographic factors. METHODS: This retrospective, interventional, consecutive case series study included subjects with different forms of subfoveal CNV. All patients received PDT-V according to Treatment of Age-Related Macular Degeneration With Photodynamic Therapy/Visudyne in Photodynamic Therapy guidelines. A review of medical and angiographic records was performed. RESULTS: Two hundred sixteen patients were divided into 4 study groups: group I, 60 eyes with classic CNV; group II, 56 eyes with predominantly classic CNV; group III, 42 eyes with minimally classic CNV; and group IV, 58 eyes with occult CNV. In groups I and II, best-corrected visual acuity (BCVA) was moderately decreased, without reaching a statistically noticeable level during the entire follow-up; lesion size reduction only reached significance in group I. Groups III and IV showed evident worsening of BCVA (P < 0.05), despite concomitant reduction in CNV size (statistically remarkable only for occult CNV). All study groups exhibited a significant correlation between higher baseline BCVA and better final visual outcome. In groups II and IV, smaller baseline CNV sizes also favorably influenced final BCVA. CONCLUSIONS: Standardized PDT-V minimizes deterioration of central vision only in patients with classic and predominantly classic CNV. Irrespective of the CNV type, better BCVA at presentation represents a good predictive sign. In predominantly classic and occult lesions, minor initial CNV dimension is also a positive prognostic element.

Predictive role of coagulation-balance gene polymorphisms in the efficacy of photodynamic therapy with verteporfin for classic choroidal neovascularization secondary to age-related macular degeneration.

OBJECTIVES: Age-related macular degeneration (AMD) represents the leading cause of blindness in Western populations. The majority of severe vision loss occurs in the exudative form of AMD, characterized by the development of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) represents one of the most largely employed modality that maybe achieves the subfoveal CNV inactivation in AMD patients. Although several ocular factors have been hitherto investigated as predictors, these researches have weakly contributed to PDT-V optimization. As PDT-V benefit is determined by CNV photothrombosis, we have retrospectively studied several coagulation-balance gene polymorphisms as predictors of PDT-V efficacy. METHODS: Ninety Caucasian patients with neovascular AMD were subdivided in responder and nonresponder, on the basis of CNV responsiveness to PDT-V application. Six gene polymorphisms, that is factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in the entire cohort. RESULTS: Logistic regression models showed that PDT-V responders were more prevalent within patients with prothrombin G20210A mutation [odds ratio (OR)=5.6, 95% confidence interval (CI) (1.2, 27.2), P=0.03], and within methylenetetrahydrofolate reductase 677T carriers [OR=6.9, 95% CI (2.7, 18.1), P<0.001]. Conversely, PDT-V nonresponders were overrepresented in carriers for factor XIII-A 185T [OR=0.13, 95% CI (0.05, 0.36), P<0.001]. CONCLUSION: These results provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of PDT-V effectiveness in patients with AMD-related CNV.

Increased retinal blood flow in patients with active Graves' ophthalmopathy.

PURPOSE: To investigate retinal blood flow by Heidelberg retina flowmeter in patients with active Graves' ophthalmopathy. MATERIALS AND METHODS: Thirty patients with active Graves' ophthalmopathy in euthyroid state and thirty normal controls were enrolled in this study. All subjects underwent heart rate, systolic and diastolic blood pressure detection, complete ophthalmological examination, Hertel's exophthalmometry, and retinal blood flow analysis by Heidelberg retina flowmeter. Patients additionally underwent automated threshold perimetry and extraocular muscle thickness measurement by A-scan ecography. RESULTS: A significant statistical difference was found in exophthalmometry (P<0.001), intraocular pressure (P<0.001) and retinal blood flow (P<0.05) between patients and controls. In patients, muscle enlargement was significantly correlated with retinal blood flow (r=0.49, P=0.005) and proptosis (r=0.37, P=0.04). A significant positive correlation (r=0.52, P=0.002) was also found between intraocular pressure and proptosis. CONCLUSIONS: Active Graves' ophthalmopathy patients present an increased retinal blood flow.

Effect of 2% dorzolamide on retinal blood flow: a study on juvenile primary open-angle glaucoma patients already receiving 0.5% timolol.

AIM: To investigate whether dorzolamide modifies peripapillary retinal haemodynamics in juvenile primary open-angle glaucoma (JPOAG) patients treated with timolol. METHODS: In 40 JPOAG subjects, before and after dorzolamide coadministration with timolol, the following examinations were achieved: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), heart rate (HR), visual field and retinal flowmetry. RESULTS: Adjunctive therapy with dorzolamide induced the following modifications: IOP reduction [1.75 mmHg, 95% confidence interval (CI) 1.23, 2.26; P < 0.05], OPP increase (5.09 mmHg, 95% CI 2.97, 7.20; P < 0.02) and retinal blood flow improvement (35.0 arbitrary units, 95% CI 12.20, 57.80; P < 0.03). BP, HR and visual field indices did not change. CONCLUSIONS: Dorzolamide, in association or in fixed combination with timolol, significantly improves retinal blood flow in JPOAG patients.

Prevalence of factor XIII Val34Leu polymorphism in patients affected by spontaneous subconjunctival hemorrhage.

PURPOSE: To verify the prevalence of Val34Leu polymorphism in factor XIII A-chain gene (FXIII Val34Leu) in patients with spontaneous subconjunctival hemorrhage (SCH). DESIGN: Nonrandomized case-control study. METHODS: One hundred seven white patients suffering from one or more episodes of idiopathic SCH and 107 healthy subjects were matched for age and gender, and genotyped for FXIII Val34Leu. Anamnestic, ophthalmologic, cardiovascular, and serologic examinations were performed. RESULTS: Frequency of FXIII mutated allele (Leu34) was significantly higher in SCH patients than in controls. Computing together heterozygotes (Val/Leu) and homozygotes (Leu/Leu), genotype distribution was statistically different. In a conditional logistic regression model, the comparison of the three separated genotypes, performed among 25 patients with recurrent idiopathic SCHs and controls, gave significant differences for both Val/Leu and Leu/Leu variables. CONCLUSION: Both homozygosity and heterozygosity for FXIII Val34Leu predispose to idiopathic SCH, emphasizing the role of Leu34 allele as inherited risk factor for spontaneous, especially recurrent, SCHs.