Intraocular lens dislocation and tube shunt in the posterior chamber: a case report.

BACKGROUND: To describe management of a case of intraocular lens (IOL) and capsular bag (CB) dislocation in an eye with an Ahmed glaucoma valve in the posterior chamber. CASE PRESENTATION: A 75-year-old pseudophakic man with open-angle glaucoma and diabetic retinopathy developed neovascular glaucoma. After two intravitreous injections of bevacizumab and panretinal photocoagulation were administered, the new vessels regressed. However, goniosynechiae were observed over 360° of the angle. An Ahmed glaucoma valve model FP7 was implanted with the tube in the posterior chamber with adequate intraocular pressure control. Nineteen years after cataract surgery, when the IOL-CB complex became dislocated, they were sutured transclerally to the sulcus without Ahmed glaucoma valve modification. After a coughing episode, the vitreous pushed the IOL-CB complex forward and the tube was behind the IOL-CB complex. A 25-gauge posterior vitrectomy was performed, and the tube was returned to in front of the optic of the IOL using a forceps tip through a sclerotomy. CONCLUSION: This case suggested that management of IOL-CB dislocation can modify glaucoma shunt function. A complete pars plana vitrectomy may be required in order to reposition the dislocated IOL-CB complex in the presence of a posterior chamber drainage tube implant.

Transforming growth factor-beta inhibition reduces progression of early choroidal neovascularization lesions in rats: P17 and P144 peptides.

The purpose of this study was to assess the effects of transforming growth factor beta (TGF-ß) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-ß, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3(rd) week in IVT-17 and IVT-144 groups, and also from the 2(nd) week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-ß inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single therapy or adjuvant to anti-VEGF drugs.

Effect of lutein and antioxidant supplementation on VEGF expression, MMP-2 activity, and ultrastructural alterations in apolipoprotein E-deficient mouse.

Oxidative stress is involved in the pathogenesis of several diseases such as atherosclerosis and age-related macular degeneration (AMD). ApoE-deficient mice (apoE(-/-)) are a well-established model of genetic hypercholesterolemia and develop retinal alterations similar to those found in humans with AMD. Thus supplementation with lutein or multivitamin plus lutein and glutathione complex (MV) could prevent the onset of these alterations. ApoE(-/-) mice (n = 40, 3 months old) were treated daily for 3 months with lutein (AE-LUT) or MV (two doses): AE-MV15 (15 mg/kg/day) and AE-MV50 (50 mg/kg/day) and were compared to controls with vehicle (AE-C). Wild-type mice (n = 10) were also used as control (WT-C). ApoE(-/-) mice showed higher retinal lipid peroxidation and increased VEGF expression and MMP-2 activity, associated with ultrastructural alterations such as basal laminar deposits, vacuoles, and an increase in Bruch's membrane thickness. While lutein alone partially prevented the alterations observed in apoE(-/-) mice, MV treatment substantially reduced VEGF levels and MMP-2 activity and ameliorated the retinal morphological alterations. These results suggest that oxidative stress in addition to an increased expression and activity of proangiogenic factors could participate in the onset or development of retinal alterations of apoE(-/-) mice. Moreover, these changes could be prevented by efficient antioxidant treatments.

Comparative study measuring the dilatory effect of a mydriatic device (Mydriasert(®)) versus topical drops.

AIM: To compare the mydriatic efficacy of an ophthalmic insert (Mydriasert, MY) versus phenylephrine and tropicamide (PT) eye drops. METHODS: Two controlled, prospective, randomized, single-blind studies were performed. In the first study, a total of 80 eyes from 40 outpatient-clinic patients were analyzed. PT drops were applied to the right eye, and a MY device was inserted in the left eye for 30min. Time until maximal pupil dilation for each eye was then assessed. In the second study, 80 eyes from 80 patients undergoing cataract surgery were analyzed. Pupil dilation was achieved using either PT drops three-times for one hour prior to surgery (40 patients), or a MY device was inserted one hour prior to surgery (40 patients). RESULTS: In the first study, MY achieved superior mydriasis compared to PT eye drops at 90min (9.04±1.33mm vs 8.78±1.37mm, P=0.012). However MY took longer than PT drops to achieve maximal dilation, and mydriasis was inferior in eyes with MY compared to PT drops at 30min (7.21±1.73mm vs 8.22±1.43mm, P<0.001), the two groups only becoming similar by 60min (8.85±1.44mm vs 8.71±1.27mm, P=0.236). In the second study, both MY and PT achieved similar levels of mydriasis at the beginning of surgery (8.75±0.76mm with MY vs 8.77±0.63mm with PT), and also at the end of surgery (7.96±1.06mm with MY vs 8.32±0.72mm with PT), with no significant difference between groups (P=0.08). MY was well tolerated and cardiovascular effects were not influenced by dilation method. CONCLUSION: MY could be a safe and efficacious alternative for mydriasis. The mydriatic effect of MY is as good as conventional PT eye drops after 60min, and is superior after 90min. MY also maintains good pupil dilation during cataract surgery.

Transforming growth factor-ß inhibition decreases diode laser-induced choroidal neovascularization development in rats: P17 and P144 peptides.

PURPOSE: To assess the effect of transforming growth factor (TGF)-ß inhibitor peptides (P17 and P144) on the development of laser-induced choroidal neovascularization (LI-CNV) in a rat model. METHODS: Sixty-one Long-Evans rats underwent diode LI-CNV model. Forty-eight hours later, treatment was administered. The intravenous control group (IV-control) and intravenous P17 group (IV-17) received five doses (0.2 mg every 72 hours) of vehicle and P17, respectively. Four groups received intravitreal injections of P17 low-dose (LD-17; 1 mg/mL) and high-dose (HD-17; 20 mg/mL) and P144 low-dose (LD-144; 1 mg/mL) and high-dose (HD-144; 3 mg/mL), and fellow eyes received vehicle. CNV evolution was assessed weekly by fluorescein angiography (FA). After death, VEGF, TGF-ß and PDGF protein levels were measured by ELISA in RPE and retina homogenates. Data were analyzed with commercially available statistical analysis software. RESULTS: The mean CNV area, measured in pixels, was significantly lower at the second and fourth weeks in IV-17 (P < 0.05) and from the second week in HD-17 (P < 0.05), whereas LD-144 and HD-144 showed significant differences at every time point (P < 0.05). LD-17 showed significantly lower protein levels of TGF-ß in retina and PDGF in RPE (P < 0.05), whereas HD-17 showed lower levels of VEGF (RPE and retina; P < 0.05), TGF-ß (RPE and retina; P < 0.05), and PDGF (RPE; P < 0.05). HD-144 showed lower VEGF levels in the retina (P < 0.05). CONCLUSIONS: TGF-ß inhibition with these peptides represents a promising new therapeutic line for CNV targeting a different pathway than current therapies. More studies are needed to assess this effect on early CNV, alone or in combination with anti-VEGF.

Intravitreal bevacizumab associated with grid laser photocoagulation in macular edema secondary to branch retinal vein occlusion.

PURPOSE: To evaluate intravitreal bevacizumab (IVB) combined with grid laser photocoagulation in macular edema (ME) secondary to branch retinal vein occlusion (BRVO). METHODS: Eight eyes (8 patients) with ME associated with BRVO with at least 3 months of evolution since symptom onset were included. All subjects underwent measurement of best-corrected visual acuity (BCVA) and imaging with spectral domain optical coherence tomography (SD-OCT) at baseline and 1, 3, 6, and 12 months. Intravitreal bevacizumab was administered at baseline and macular grid laser photocoagulation 1 month later. During follow-up, additional IVB was administered based on physician discretion if persistent or recurrent intraretinal fluid (cysts) was observed on SD-OCT. The mean BCVA and SD-OCT central subfield thickness (CST) values were determined at each time point. Fisher exact test was performed to assess differences between baseline and post-treatment BCVA and SD-OCT measurements. RESULTS: The mean baseline BCVA was 0.28±0.14 (mean±SD), and the mean CST was 479±137 µm. The mean BCVAs at 1, 3, 6, and 12 months were 0.47±0.18 (p=0.031), 0.56±0.50 (p=0.031), 0.65±0.60 (p=0.008), and 0.66±0.65 (p=0.016), respectively. The mean CST values at 1, 3, 6, and 12 months were 295±60 µm (p=0.008), 333±114 µm (p=0.070), 339±80 µm (p=0.008), and 335±109 µm (p=0.008). A mean 2.13 injections were administered; the second injection was administered a mean of 2.71 months after baseline. CONCLUSIONS: Combined treatment with IVB and macular grid photocoagulation provided good results and may be considered as an alternative therapy for ME in BRVO. Further studies are needed to assess these preliminary results.

Prevalence and causes of bilateral blindness and visual impairment among institutionalized elderly people in Pamplona, Spain.

PURPOSE: To estimate the prevalence and causes of bilateral blindness and visual impairment in an urban institutionalized population aged 65 years and older. METHODS: A total of 392 nursing home residents completed a standardized eye examination, including measurement of visual acuity (VA), intraocular pressure, lens opacity grading, indirect ophthalmoscopy, and photography of the macular area. The major causes of vision loss identified for all participants were blindness and visual impairment. RESULTS: The average subject age was 82 years (65-97); women outnumbered men 263 to 129. The prevalence of bilateral blindness (VA > or =1.0 logarithm of the minimum angle of resolution [logMAR]) was 14.9% (43/288); the prevalence of visual impairment (VA > or =0.5 and 1.0 logMAR) was 31.9% (92/288). Blindness and visual impairment increased significantly with age (p<0.05), odds ratio (OR) 1.047 and 1.088, respectively. Cataract was the most common cause of bilateral blindness and visual impairment (27.9% and 44.6%, respectively) followed by pathologic myopia (23.3%) and age-related macular degeneration (AMD) (20.9%) for blindness, and by AMD (27.2%) and pathologic myopia (12%) for visual impairment. Fifty percent of subjects with visual loss had the potential for improved vision with medical or surgical intervention. CONCLUSIONS: Although the prevalences were high, these data are important since it is difficult for epidemiologic studies to include aged, institutionalized individuals, although their numbers are increasing. Recognition of the predominant causes of visual loss dependent on age is fundamental for early diagnosis and treatment of ocular diseases. Many cases of low vision can be treated with appropriate ophthalmologic care.

Effect of zeaxanthin and antioxidant supplementation on vascular endothelial growth factor (VEGF) expression in apolipoprotein-E deficient mice.

PURPOSE: Apolipoprotein E(-/-) deficient (apoE(-/-)) mice develop hypercholesterolemia, atherosclerosis, and retinal alterations. We studied the oxidative status and vascular endothelial growth factor (VEGF) expression in murine retinal pigment epithelium-choroid (RPE) and Bruch's membrane (BM) ultrastructure and the effect of zeaxanthin. METHODS: Ten 6-month-old C57BL/6 and 40 apoE(-/-) mice were divided into four groups (n = 10 each) and fed different diets for 12 weeks based on body weight: wild type (WT) and apoE(-/-) (AE-Con) mice standard rodent chow; apoE(-/-) mice (AES) standard rodent chow with ascorbate (800 mg/kg), tocopherol (1053 mg/kg), and zinc (135 mg/kg); and apoE(-/-) mice the last diet plus zeaxanthin with either 0.4 g/kg (AES-Z04) or 4 g/kg feed (AES-Z4). RESULTS: Plasma total cholesterol (TC) and triglycerides (TG) and urine lipid peroxidation (isoprostanes) were measured. VEGF expression was determined in RPE-choroid homogenates. Zeaxanthin uptake was assessed in liver and retina by high-performance liquid chromatography; the retinal ultrastructure was analyzed by electron microscopy. AE-Con mice had higher plasma TC (p < 0.001) and TG (p < 0.001) values than WT mice. AE-Con mice had higher RPE-choroid-VEGF levels than WT mice (p < 0.05), BM thickness (p < 0.001) and presence of basal laminar deposits (BLamD). AES-Z4 resulted in lower urinary isoprostanes (p = 0.054) and lower VEGF expression in the RPE-choroid (p < 0.01). BM in the AES-Z4 animals had less confluent BLamD than AE-Con, AES, or AES-Z04 animals. CONCLUSIONS: We have reported that supplementation with zeaxanthin and antioxidants may delay or reverse alterations in the RPE and deposits in BM, and reduced VEGF expression observed in apoE(-/-) mice.

Development of laser-induced choroidal neovascularization in rats after retinal damage by sodium iodate injection.

PURPOSE: To determine the role of the retinal pigment epithelium (RPE) in the development of laser-induced choroidal neovascularization (CNV) by selective damage with sodium iodate (SI). METHODS: In group 1, diode laser photocoagulation was applied to the right eye of Long-Evans rats (n = 11). In group 2 (n = 11), SI was administered intravenously at a dose of 40 mg/kg of body weight 2 days after photocoagulation. In group 3 (n = 10), SI was injected 2 days before laser was applied. In group 4 (n = 10), SI was injected immediately after photocoagulation. RESULTS: CNV ingrowth developed in 42 of 93 burns (45%) of the laser group and in 46 of 75 burns (61%) when SI was administered 2 days after laser (p = 0.036). No CNV developed in the other groups. CONCLUSIONS: The angiogenic effect of the RPE is essential during the first hours after the onset of the laser-induced CNV process. When the RPE was damaged before or at the time of photocoagulation, CNV was not induced. These results suggest that RPE integrity is a decisive element in CNV formation.

Laser refractive surgery in a patient with a prepapillary arterial loop.

PURPOSE: To present a patient with a prepapillary vascular loop, a congenital anomaly that has been associated with vitreous hemorrhage and retinal vascular occlusion, who underwent refractive surgery. METHODS: A 45-year-old man with 2.00 diopters (D) of myopia and a unilateral prepapillary arterial loop presented with an interest in LASIK. After consideration of the theoretical risks of LASIK, the patient underwent photorefractive keratectomy with manual de-epithelialization and a scanning spot excimer laser. RESULTS: Postoperatively, uncorrected visual acuity was 20/20, visual field testing was normal, and no complications occurred. Follow-up was 4 years. CONCLUSIONS: Surface ablation was a safe method in a low myopic patient with a prepapillary vascular loop. This case emphasizes the importance of a thorough vitreoretinal examination in laser refractive candidates.

Diagnostic accuracy of retinal abnormalities in predicting disease activity in MS.

OBJECTIVES: To assess the association between the thickness of the retinal nerve fiber layer (RNFL), assessed by optical coherence tomography (OCT), retinal periphlebitis (RP), and multiple sclerosis (MS) disease activity. METHODS: We studied a prospective cohort of 61 patients and 29 matched controls for 2 years, performing a neurologic assessment every 3 months and an ophthalmologic evaluation, including OCT scans, every 6 months. Baseline MRI studies were also carried out from which brain volume and lesion load were assessed. RESULTS: We found that the RNFL thickness in patients with MS was thinner than in controls, particularly in the temporal quadrant (p = 0.004). Although RNFL atrophy was greater in patients who also had optic neuritis (p = 0.002), it also augmented in MS patients who did not have optic neuritis compared with controls (p = 0.014). RNFL atrophy was correlated with greater disability (r = -0.348, p = 0.001) and longer disease duration (r = -0.301, p = 0.003). Furthermore, baseline temporal quadrant RNFL atrophy was associated with the presence of new relapses and changes in the Expanded Disability Status Scale by the end of the study (p < 0.05 in all cases). Indeed, RNFL thickness was correlated with white matter volume (r = 0.291, p = 0.005) and gray matter volume (r = 0.239, p = 0.021). The presence of RP was a risk factor for having new relapses in the next 2 years (odds ratio = 1.52, p = 0.02), and patients with RP had larger gadolinium-enhancing lesions volume (p = 0.003). CONCLUSION: Retinal nerve fiber layer atrophy and the presence of retinal periphlebitis are associated with disease activity, suggesting that retinal evaluation can be used as biomarkers of multiple sclerosis activity.

Using optical coherence tomography to monitor photodynamic therapy in age related macular degeneration.

PURPOSE: To evaluate the role of optical coherence tomography (OCT) in determining choroidal neovascularization (CNV) activity before and after photodynamic therapy (PDT) in patients with age-related macular degeneration (ARMD). DESIGN: Prospective observational case series. SETTING: Institutional study. patient population: Fifty-three patients (62 eyes) with ARMD. OBSERVATION PROCEDURE: Prospective observational case study. MAIN OUTCOME MEASURES: Presence or absence of leakage on fluorescein angiography, presence of intraretinal or sub-retinal fluid on OCT, and macular and choroidal neovascular complex thickness on OCT. RESULTS: The macular thickness decreased significantly after PDT (P = .001). However, no significant changes in CNV thickness were measured after PDT (P = .567). Once the diagnosis of ARMD was established before treatment, OCT had a sensitivity of 96.77% for detecting CNV activity. After treatment, OCT had a good sensitivity (95.65%) and a moderate specificity (59.01%) in determining CNV activity, which resulted in a diagnostic efficiency (proportion of correct results) of 82.95%. CONCLUSIONS: OCT appears to be useful for indicating CNV activity. Therefore, it may serve as a complementary technique for deciding the need for PDT and re-treatment in patients with ARMD.