Disc-foveal angle and ocular counterrolling as a key in its interpretation. / El ángulo papila-fóvea y la torsión ocular compensatoria, clave en su interpretación.

PURPOSE: Describe a time-sparing technique to measure disc-foveal angle (DFA), determine normal values and its role when analyzing paired fundus photographs. METHODS: DFA was analysed using the software program Keynote v.6.2.2 on 440 fundus photographs (3D OCT 2000, Topcon Corporation, Tokio, Japan) of 20 individuals. The 11 different head positions were determined with the cervical range of motion device (CROM, Performance Attainment Associates). A reproducibility and correlation study between two fundus cameras (OCT 3D-2000 and TRC-50EX, Topcon Corporation, Tokio, Japan) was performed. RESULTS: Mean DFA of the right and left eye was 5.5±3.4° and 8.6±2.9°, with a difference of 3.1° (P=0.001 Wilcoxon signed-rank test) in the upright head position. Mean absolute difference in DFA between eyes was 3.5±2.6°; an increase was seen with increasing head tilt (P=0.000 Wilcoxon signed-rank test). Mean sum of DFA in both eyes was 14.1±5.4°. On head-tilt of 20° and 40° to the right, mean ocular counterrolling (OCR) was 7.1° and 12.2° in the right eye and 7.7° and 12.1° in the left eye. On head-tilt of 20° and 40° to the left, OCR was 4.4° and 8° in the right eye and 4.2° and 8.7° in the left eye (P=0.000 Wilcoxon signed-rank test). The two cameras showed strong correlation and high reproducibility. CONCLUSIONS: Our DFA measurement technique is time-sparing and reproducible. Left eye shows higher DFA than right eye. OCR occurs only in the roll plane. This information is of value when analyzing paired fundus photographs.

Management of Wet Age-Related Macular Degeneration in Spain: Challenges for Treat and Extend Implementation in Routine Clinical Practice.

PURPOSE: To ascertain wet AMD (wAMD) management patterns in Spain. METHODS: A two-round Delphi study conducted through a questionnaire-based survey designed from literature review and validated by an independent Steering Committee. RESULTS: Forty-nine retina specialists experienced in wAMD participated by answering the two-round study questionnaire. Retina specialists are the main responsible for wAMD diagnosis and monitoring, including visits and associated procedures, with a median time per visit of 15 minutes. Standard treatment strategies are based on anti-VEGF administration, including standard loading dose administration followed by maintenance with aflibercept or ranibizumab (81% of patients). Although treat and extend (T&E) dosing strategy is considered as optimal for wAMD management (78% of the panelists), the main routine healthcare limitations (i.e., visits overload, reduced staff, short visit time, coordination issues, lack of facilities) conduct to self-defined "flexible" strategies, based on T&E and pro-re-nata (PRN) protocols. CONCLUSION: Proactive treatment patterns (T&E) are the preferred ones by the retina specialists in Spain. However, their proper implementation is difficult due to healthcare resource limitations, as well as organisation and logistic issues. The use of anti-VEGF agents with longer duration of action could facilitate the use of strict T&E approaches according to routine clinical practices.

Efficacy of immunomodulatory therapy with interferon-ß or glatiramer acetate on multiple sclerosis-associated uveitis. / Eficacia del tratamiento inmunomodulador con interferón-ß o acetato de glatirámero en las uveítis asociadas a esclerosis múltiple.

AIM: To analyse the role of interferon-ß or glatiramer acetate in reducing the inflammatory episodes of intra-ocular inflammation in multiple sclerosis-associated uveitis. METHOD: A study was conducted on a non-randomised, retrospective case series of 13 patients with proven multiple sclerosis and uveitis (minimum follow-up, 12 months). All patients were given immunomodulatory treatment (interferon-ß or glatiramer acetate) to control the course of the multiple sclerosis. Patients were compared to themselves before initiating the treatment, in order to assess the difference in uveitis episodes. The main outcome measurements were the number of uveitis episodes with/without immunomodulatory treatment. RESULTS: Uveitis was bilateral in 10 (77%) out of 13 patients. Intermediate uveitis was observed in 11 patients, retinal vasculitis in 3 patients, and one patient was classified as a posterior uveitis. The patients had a mean of 4.15±3.1 episodes of uveitis (range 1-10) during the follow-up period (148.6±84.3 months). When compared to their pre-treatment status, patients on treatment with interferon-ß or glatiramer acetate showed a significant decrease of 0.36 episodes of ocular inflammation per year (P=.02). Mild side effects related to immunomodulatory treatment were observed in 6 (46%) patients, 3 (23%) patients with a flu-like syndrome, and 3 (23%) patients with a skin rash. CONCLUSIONS: Interferon ß or glatiramer acetate could be effective in reducing the uveitis episodes in patients with multiple sclerosis-associated uveitis, and was well tolerated in most patients.

[Intravitreal bevacizumab for choroidal neovascularization associated with Best's disease]. / Bevacizumab intravítreo en neovascularización coroidea asociada a enfermedad de Best.

CASE REPORT: A 27-year old woman presented with loss of vision in the right eye (20/200). Ophthalmoscopic examination showed intrarretinal hemorrhage in the macular region with neurosensory detachment in the right eye, and viteliform deposit on the left eye. Fluorescein angiography and the electrooculogram confirmed the diagnosis of choroidal neovascularization associated with Best's disease. Four weeks after a single bevacizumab intravitreal injection, visual acuity was restored (20/25) and remained stable after a 12 month follow-up. DISCUSSION: Intravitreal bevacizumab appears to be an effective treatment for choroidal neovascularization associated to Best's disease.

Cyclodialysis induced persistent hypotony: surgical management with vitrectomy and endotamponade.

PURPOSE: To report novel surgical approaches to the management of persistent hypotony after cyclodialysis. METHODS: Retrospective review of the medical records of six eyes of six patients with persistent hypotony after traumatic cyclodialysis. The diagnosis accuracy of cyclodialysis was documented by ultrasound biomicroscopy in five patients. The other one underwent an anterior segment optical coherence tomography. The authors performed pars plana vitrectomy and silicone oil-assisted endotamponade in four patients. The remaining eyes underwent a gas tamponade after pars plana vitrectomy. RESULTS: Preoperative visual acuity (Snellen scale) ranged from count fingers to 20/50. The patients' visual acuity improved after the surgery. The intraocular pressure ranged from 2 mmHg to 6 mmHg (mean, 3.33 mmHg) before surgery. The authors did achieve an intraocular pressure normalization postoperatively. After surgery, the ciliary body was completely reattached in all cases. A slight angle recession was documented in one eye. CONCLUSION: The management of cyclodialysis clefts requires a stepwise approach. In cases where conservative management fails, wide ranges of options have been reported. Based on our results, we consider that silicone oil-assisted or gas-assisted endotamponade, after pars plana vitrectomy, can be an effective alternative approach to the cyclodialysis.

Rhegmatogenous retinal detachment treatment guidelines.

This paper outlines general guidelines following the initial diagnosis of rhegmatogenous retinal detachment. These include preoperative evaluation, treatment, possible intra- and post-operative complications, retinal re-detachment, and all therapeutic options available for each case. Treatment of the traumatic retinal detachment is also described, due to its importance and peculiarities. Treatment or prophylactic guidelines are suggested for the different types of retinal detachment described. These are based on both the experience of the ophthalmologists that have participated in preparing the guidelines, and also on evidence-based grading linked to bibliographical sources. However, these guidelines should not be interpreted as being mandatory. Given that there is a wide spectrum of options for treatment of retinal detachment, the surgeons' experience with one or other surgical technique will be of utmost importance in obtaining the best surgical result. As guidelines, they are intended as an additional aid to the surgeon during the decision-making process, with the expectation that the final choice will still be left to the surgeon's judgment and past experience.

[Best's vitelliform macular dystrophy associated with choroidal neovascularization]. / Distrofia macular viteliforme de Best asociada a neovascularización coroidea.

CASE REPORT: We report the case of a child with a sudden loss of vision of the left eye. Ophthalmoscopic examination revealed vitelliform lesions in both foveal centers, as well as an adjacent hemorrhage in his left eye. Fluorescein angiography confirmed the presence of a neovascular membrane in his left eye. The electrooculogram showed disease. According to complementary studies the patient was diagnosed with Best's disease associated with choroidal neovascularization. DISCUSSION: The diagnosis of Best's vitelliform macular dystrophy is often a casual finding as visual acuity tends to remain stable for long periods of time. A sudden deterioration in vision may suggest complications, such as choroidal neovascularization.

Vitreous levels of somatostatin in patients with chronic uveitic macular oedema.

PURPOSE: Intravitreal somatostatin (SST) levels are decreased in patients with diabetic macular oedema. This deficit may be involved in the pathogenesis of this condition. The aim of the present study was to determine SST concentration in the vitreous fluid of patients with chronic uveitic macular oedema (CUMO) and quiescent intraocular inflammation. METHODS: Plasma and vitreous fluid samples were obtained during vitrectomy from 11 eyes of patients with CUMO and from 42 eyes of control subjects (idiopathic epiretinal membrane, macular hole). SST concentration was measured by radioimmunoassay. STATISTICS: χ(2)-square test, Mann-Whitney U-test, Wilcoxon test, Spearman's rank correlation coefficient, and multivariant linear regression models. RESULTS: Plasma SST concentrations were similar in uveitic patients and controls (28.25 pg/ml (21.3-31) vs 28.7 pg/ml (22-29.5); P=0.869). A higher vitreous concentration of proteins was found in uveitic patients (1.59±0.38 mg/ml vs 0.73±0.32 mg/ml, P<0.0001). Vitreous SST was markedly lower in uveitic patients, both in absolute terms and after adjusting for total intravitreous protein concentration (39.37 pg/ml (6.16-172) vs 486.73 pg/ml (4.7-1833), P<0.0001; 33.1 pg/mg (3.9-215.74) vs 629.75 pg/mg (6.91-2024), P<0.0001). No correlations were found between plasma and vitreous concentration of SST in either group (ρ=0.191, P=0.57 and ρ=0.49, P=0.66). There were no correlations between vitreous SST concentration and visual acuity or macular thickness in uveitic patients (ρ=0.302, P=0.31 and ρ=0.45, P=0.13). CONCLUSIONS: Intravitreous SST is decreased in patients with CUMO and quiescent intraocular inflammation. The deficit of SST may have a role in the pathogenesis of this condition.

[From scientific evidence to clinical practice: treatment regimens for macular edema secondary to retinal vein occlusion]. / De la evidencia cientifica a la practica clinica: pautas de tratamiento del edema macular secundario a oclusion venosa retiniana.

Retinal vein occlusion (RVO) is the second most common cause of retinal vascular disease after diabetic retinopathy. Despite the existence of several possible treatment options, none was entirely satisfactory and many patients suffered irreversible visual loss. As a result of the BRAVO, CRUISE and GENEVA trials, ranibizumab and the intravitreal biodegradable implants of dexamethasone has recently been approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of RVO secondary edema. In this paper we begin by describing the current treatment options for RVO associated macular edema and continue with the description of the treatment regimen with ranibizumab.

Vitreous levels of interleukine-8 and monocyte chemoattractant protein-1 in macular oedema with branch retinal vein occlusion.

PURPOSE: To investigate whether interleukine-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are related with macular oedema in patients with branch retinal vein occlusions (BRVOs). DESIGN: Retrospective case-control study. PARTICIPANTS: Nineteen patients who had macular oedema due to BRVO and nine patients with non-ischaemic ocular diseases (control group). METHODS: Macular oedema was examined by optical coherence tomography. Both venous blood and vitreous samples were obtained at the time of vitreoretinal surgery. IL-8 and MCP-1 levels in vitreous fluid and plasma were determined with enzyme-linked immunosorbent assay kits. Variables were compared with the Mann-Whitney U-test, Wilcoxon's signed-ranked test, and the chi2-test, when appropriate. To examine correlations, Spearman's rank-order correlation coefficients were calculated. Statistical significance was set at P<0.05. RESULTS: The vitreous fluid levels of IL-8 (median: 63.5 pg/ml) and MCP-1 (median: 1522.4 pg/ml) were significantly higher in the patients with BRVO than in the control group (median: 5.1 and 746.5 pg/ml respectively; P<0.001 and <0.001 respectively). Vitreous IL-8 and MCP-1 were significantly correlated in patients with BRVO (P=0.009). CONCLUSIONS: Both IL-8 and MCP-1 were elevated in the vitreous fluid of patients with BRVO and macular oedema. Both chemokines may contribute to the pathogenesis of macular oedema in patients with BRVO.

Interphotoreceptor retinoid-binding protein (IRBP) is downregulated at early stages of diabetic retinopathy.

AIMS/HYPOTHESIS: Interphotoreceptor retinoid-binding protein (IRBP) plays a major role in the visual cycle and is essential to the maintenance of photoreceptors. The aim of this study was to determine whether a decrease in IRBP production exists in the early stages of diabetic retinopathy. METHODS: Vitreous samples from diabetic patients with proliferative and non-proliferative diabetic retinopathy (PDR, NPDR), and from non-diabetic patients with macular hole (control group) were selected for IRBP quantitative assessment by proteomic analysis (fluorescence-based difference gel electrophoresis) and western blot. Human post mortem eyes (n = 16) from diabetic donors without clinically detectable retinopathy and from non-diabetic donors (n = 16) were used to determine IRBP (also known as RBP3) mRNA levels (RT-PCR) and protein content (western blot and confocal microscopy). Retinal neurodegeneration was assessed by measuring glial fibrillar acidic protein (GFAP) and the apoptotic rate. Y79 human retinoblastoma cells were used to test the effects of glucose, TNF-alpha and IL-1beta on IRBP expression and IRBP levels. RESULTS: Intravitreous IRBP concentration was significantly lower in PDR < NPDR < control in proteomic and western blot analysis. IRBP mRNA levels and IRBP protein content were significantly lower in the retinas from diabetic donors than in those from non-diabetic donors. Increased GFAP and a higher degree of apoptosis were observed in diabetic retinas compared with non-diabetic retinas. A dose-dependent downregulation of IRBP mRNA expression and IRBP content was detected with glucose, TNF-alpha and IL-1beta in cultures of Y79 human retinoblastoma cells. CONCLUSIONS/INTERPRETATION: Underproduction of IRBP is an early event in the human diabetic retina and is associated with retinal neurodegeneration. The mechanisms leading to this deficit deserve further investigation.

Conjunctival cytology in floppy eyelid syndrome: objective assessment of the outcome of surgery.

AIMS: Upper eyelid shortening is the main surgical procedure in floppy eyelid syndrome (FES). The efficacy of surgery is assessed by improvements in the symptoms, since objective evaluation is difficult. Conjunctival impression cytology was assessed as an objective method for the evaluation of the effectiveness of surgery for FES. METHOD: The study was a prospective interventional study in 16 patients (26 eyelids) with FES, who were enrolled over a period of 8 months. Patients were examined 1-4 weeks before surgery and 16 weeks after surgery. Cases were classified into three groups according to the severity of symptoms and papillary reaction. A full-thickness pentagonal wedge resection was performed in the upper eyelid. Impression cytology was performed in all patients at 1-4 weeks before surgery and 16 weeks after surgery. RESULTS: Postoperative improvements in cellular morphology and goblet cell count were found in 20 of 22 eyelids (91%) and this led to a decrease of least one grade in Nelson's classification. In two cases (9%) the Nelson grade remained stable. Postoperative improvement on cytology was statistically significant with the Wilcoxon signed ranks test (p<0.001). CONCLUSION: Conjunctival cytology provides an objective method for the evaluation of the efficacy of surgical techniques proposed for the treatment of eyelid laxity syndromes.

Vitreous levels of erythropoietin in patients with macular oedema secondary to retinal vein occlusions: a comparative study with diabetic macular oedema.

OBJECTIVE: In a recent study, we found high levels of erythropoietin (EPO) in patients with diabetic macular oedema (DME), suggesting a role of EPO in the pathogenesis of this condition. To investigate a possible relationship between EPO and other diseases causing macular oedema, we determined vitreous levels of this peptide in patients with macular oedema secondary to retinal vein occlusion (RVO) and compared them with levels in patients with DME and control patients. METHODS: Vitreous and serum samples were obtained from patients with macular oedema secondary to RVO, DME, epiretinal membrane, and macular hole (controls). EPO was measured by radioimmunoassay. RESULTS: No differences were found in median vitreous EPO levels between patients with RVO and controls: RVO, 76 mU/ml (30-806) vs controls, 25 mU/ml (10-75) (P=0.105). Median EPO concentration was higher in DME patients than in patients with RVO or controls: DME, 430 mU/ml (41-3000) vs RVO, 76 mU/ml (30-806) (P<0.0001) vs controls, 25 mU/ml (10-75) (P<0.0001). CONCLUSIONS: EPO levels are not elevated in patients with macular oedema secondary to RVO. Patients with DME have high levels of EPO. These results suggest that EPO could be involved in the pathogenesis of diabetic retinopathy, but not in macular oedema secondary to RVO.

Delay in treating age-related macular degeneration in Spain is associated with progressive vision loss.

PURPOSE: To assess the impact on visual acuity of delays between diagnosis and treatment in patients with subfoveal neovascular age-related macular degeneration (NV-AMD) and to evaluate NV-AMD patients' emotional status before therapy initiation. METHODS: This retrospective, multicenter, epidemiological study included newly diagnosed NV-AMD patients registered in the Spanish national health system and referred to regional health centers for evaluation/treatment by a retinal specialist from 09/2005 to 03/2006. Records were reviewed and data abstracted at referring physicians' offices (diagnosis visit) and regional health centers (treatment visit). Treatment was at physicians' discretion. The Hospital Anxiety and Depression Scale was administered at the treatment visit (before therapy). RESULTS: Median time from the diagnosis to treatment visit was 2.3 months (95% confidence interval: 0.2-10.8 months). Vision loss had progressed at the treatment visit with a doubling in the percentage of patients with a visual acuity of 20/400 or worse (from 12.4 to 24.7%). The decrease in visual acuity from the diagnosis to the treatment visit was highly statistically significant (P<0.0001) as was the correlation between months to treatment and visual acuity change (r=0.5234, P<0.0001). Time from the diagnosis to the treatment visit remained a significant predictor of progressive vision loss when visual acuity at diagnosis and change in lesion size between diagnosis and treatment were controlled (P<0.0001). Patients with more severe vision loss prior to treatment tended to report more depression. CONCLUSIONS: Delayed treatment of patients newly diagnosed with NV-AMD is associated with substantial visual acuity loss.

Removal of retained subretinal perfluorocarbon liquid.

AIM: To report a case series in which a modified technique was used to remove retained subretinal perfluorocarbon liquid. METHOD: In three patients with retained subretinal perfluorocarbon liquid, a three-port pars plana vitrectomy approach was used to perform a small self-sealing retinotomy adjacent to the perfluorocarbon liquid bubble. The tip of a 50-G glass micropipette connected to an active suction system was inserted in the bubble, and the liquid was aspirated. RESULTS: Successful removal of subretinal perfluorocarbon liquid was achieved in all cases with no complications. Visual acuity improved in all patients. CONCLUSION: With the technique presented, retained subretinal perfluorocarbon liquid can be successfully removed with minimal trauma to adjacent tissues.

Vitreoretinal surgery without schisis cavity excision for the management of juvenile X linked retinoschisis.

Juvenile X linked retinoschisis (XLRS) is a congenital X linked recessive retinal disorder characterised by cystic maculopathy and peripheral schisis. This study presents the case of an 8-month-old boy with a documented positive family history of XLRS, with a large retinoschisis cavity affecting the macula, first in the left eye and 1 year later in the right eye. The patient underwent pars plana vitrectomy in both eyes using 23-G instruments, posterior hyaloid dissection, a small retinotomy, fluid drainage with a 42-G cannula, infrared diode laser and silicone oil as internal tamponade. The anatomical and functional outcomes at 3 years following the first surgery are described. To the authors' knowledge, there is no previously reported experience with this technique in patients with XLRS.