Microscope-Assisted Episcleral Surgery with Encircling Buckles and Chandelier Endoillumination for Primary Rhegmatogenous Retinal Detachment in Phakic and Pseudophakic Patients: A 12-Month Comparative Study.

INTRODUCTION: The aim of the study was to compare postoperative outcomes after microscope-assisted encircling buckle and chandelier endoillumination for primary rhegmatogenous retinal detachment (RRD) in phakic and pseudophakic (PFK) patients. METHODS: 121 eyes of 117 patients were divided into 2 groups depending on the lens status (group 1, PFK, 53 eyes; group 2, phakic, 68 eyes). The main outcomes include retinal reattachment rate (RRR) and best-corrected visual acuity (BCVA) at 1 week, 1, 3, 6, and 12 months. RESULTS: The overall primary RRR was 91.7% (111/121). In group 1, the primary RRR was 90.6% (48/53), whereas in group 2 it was 92.6% (63/68). The mean preoperative BCVA improved in both groups at 12 months. Undetected retinal breaks were found in 9.9% of cases. When an encircling 5-mm oval sponge was used, no additional exoplants were required and transcleral drainage was performed in 89.7% of the eyes. In group 1, among the 5 PFK eyes with persistent RRD, 4 eyes had a sulcus intraocular lens. CONCLUSIONS: Microscope-assisted episcleral surgery with chandelier endoillumination is an effective technique for primary RRD in both phakic and PFK eyes with uncomplicated cataract surgery. Chandelier endoilluminators help to visualize undetected retinal breaks, especially in PFK eyes. In case of a circumferential 5-mm oval sponge, additional exoplants are not required and transcleral drainage is strongly recommended to flatten the retina by closing the causative breaks.

Anti-Vascular Endothelial Growth Factors Protect Retinal Pigment Epithelium Cells Against Oxidation by Modulating Nitric Oxide Release and Autophagy.

BACKGROUND/AIMS: the anti-vascular endothelial growth factors (VEGF), Aflibercept and Ranibizumab, are used for the treatment of macular degeneration. Here we examined the involvement of nitric oxide (NO), mitochondria function and of apoptosis/autophagy in their antioxidant effects in human retinal pigment epithelium cells (RPE). METHODS: RPE were exposed to Ranibizumab/Aflibercept in the absence or presence of NO synthase (NOS) inhibitor and of autophagy activator/blocker, rapamicyn/3-methyladenine. Specific kits were used for cell viability, NO and reactive oxygen species detection and mitochondrial membrane potential measurement, whereas Western Blot was performed for apoptosis/ autophagy markers and other kinases detection. RESULTS: In RPE cultured in physiological conditions, Aflibercept/Ranibizumab increased NO release in a dose and time-dependent way. Opposite results were obtained in RPE pretreated with hydrogen peroxide. Moreover, both the anti-VEGF agents were able to prevent the fall of cell viability and of mitochondrial membrane potential. Those effects were reduced by the NOS inhibitor and 3-methyladenine and were potentiated by rapamycin. Finally, Aflibercept and Ranibizumab counteracted the changes of apoptosis/autophagy markers, NOS, Phosphatidylinositol-3-Kinase/Protein Kinase B and Extracellular signal-regulated kinases 1/2 caused by peroxidation. CONCLUSION: Aflibercept and Ranibizumab protect RPE against peroxidation through the modulation of NO release, apoptosis and autophagy.

The spectrum of ocular alterations in patients with ß-thalassemia syndromes suggests a pathology similar to pseudoxanthoma elasticum.

PURPOSE: To determine the prevalence and spectrum of ocular fundus abnormalities in patients with ß-thalassemia and to investigate risk factors for their development. DESIGN: Cross-sectional, observational study. PARTICIPANTS: A total of 255 patients with ß-thalassemia major (TM) and ß-thalassemia intermedia (TI) were consecutively recruited and investigated. METHODS: Patients underwent best correct visual acuity, indirect ophthalmoscopy, and fundus photography, including fundus autofluorescence (FAF) and near-infrared reflectance imaging using a confocal scanning laser ophthalmoscope (cSLO). Hematologic parameters were determined, including mean ferritin levels, aspartate amino transferase, alanine amino transferase, calcium, pre-transfusion hemoglobin, history of splenectomy, and liver iron concentration. Factors associated with the ocular phenotype were assessed using logistic regression. MAIN OUTCOME MEASURES: Ocular phenotype as determined by clinical examination and used multimodal imaging. RESULTS: A total of 153 patients (60.0%) affected by TM and 102 patients (40.0%) affected by TI participated, of whom 216 (84.7%) were receiving iron-chelating therapy. Ocular fundus abnormalities characteristic of pseudoxanthoma elasticum (PXE) were detected by cSLO in 70 of 255 patients (27.8%) and included peau d'orange (19.6%), angioid streaks (12.9%), pattern dystrophy-like changes (7.5%), and optic disc drusen (2.0%). Pseudoxanthoma elasticum-like changes were more frequent in patients with TI (P<0.001). Patients with PXE-like fundus changes were older than patients without these fundus changes (P<0.001). In both patients with TI and TM, age (P = 0.001) and splenectomy (P = 0.001) had the strongest association with presence of PXE-like fundus changes in multivariate analyses. A total of 43 of 255 patients (16.9%) showed increased retinal vascular tortuosity independently of the PXE-like fundus changes, which was associated with aspartate amino transferase (P = 0.036), hemoglobin (P = 0.008), and ferritin levels (P = 0.005). CONCLUSIONS: Pseudoxanthoma elasticum-like fundus changes are a frequent finding in patients with ß-thalassemia. In TI, these changes increase with duration or severity of the disease. This particular ocular phenotype suggests an ocular pathology similar to PXE. Retinal vascular tortuosity may be an additional disease manifestation independent of the PXE-like syndrome. Patients with long-standing disease requiring iron-chelating treatment and a history of splenectomy need regular ophthalmic checkups because they are at risk of developing PXE-like fundus changes and potentially of subsequent choroidal neovascularization.

Structural and functional retinal changes in eyes with DUSN.

PURPOSE: To report novel spectral domain optical coherence tomography and electrophysiologic findings in diffuse unilateral subacute neuroretinitis. METHODS: Six patients with a diagnosis of diffuse unilateral subacute neuroretinitis were retrospectively ascertained. All patients had received oral treatment with albendazole; resolution of the inflammatory lesions without subsequent relapse was noted. Spectral domain optical coherence tomography was performed using a Spectralis HRA OCT (Heidelberg Engineering). The inner and outer retinal volumes were calculated for the macular area. The contralateral eyes acted as controls. All six patients underwent standardized full-field electroretinography and pattern electroretinography. Some had multifocal electroretinography. RESULTS: Inner retinal volume significantly differed between affected and control eyes (P < 0.02), but there was no significant difference in outer retinal volume. Electroretinography data showed a mixed pattern of inner and outer retinal dysfunction, with inner retinal dysfunction being greater; reduction in b:a ratio of the scotopic bright flash electroretinography was a consistent observation in those patients (5/6) with generalized retinal dysfunction. Two patients showed definite photoreceptor involvement, with probable involvement in a third. Of the four patients in whom serial data are available, there was definite evidence of progressive inner and outer retinal dysfunction in one patient, with inner retinal dysfunction being greater, and probably in a second patient. CONCLUSION: The data provide anatomical and functional evidence of both inner and outer retinal dysfunction in diffuse unilateral subacute neuroretinitis, even though the worm is usually assumed to be located in the subretinal space. The mechanism is unclear.

Multimodal imaging in deferoxamine retinopathy.

PURPOSE: To describe macular lesions in patients with deferoxamine (DFO) retinopathy, and to follow their clinical course using multimodal imaging. METHODS: The authors retrospectively reviewed charts and multimodal imaging of 20 patients with ß-thalassemia diagnosed with DFO retinopathy (40 eyes) after a minimum of 10 years of DFO treatment. Imaging included fundus photography, near-infrared reflectance and fundus autofluorescence imaging on confocal laser scanning ophthalmoscope, and spectral domain optical coherence tomography. RESULTS: Mean age of the 20 patients was 45 years, and mean duration of subcutaneous DFO therapy was 32 years (range, 20-52 years). Ten patients (50%) showed different types of pattern dystrophy-like fundus changes, including butterfly shaped-like (n = 3), fundus flavimaculatus-like (n = 3), fundus pulverulentus-like (n = 3), and vitelliform-like (n = 1) changes. Ten patients (50%) presented only minimal changes in the macula; these patients were significantly younger than patients presenting other patterns (P = 0.023). Confocal laser scanning ophthalmoscope and spectral domain optical coherence tomography showed that these abnormalities were more diverse and widespread than expected by ophthalmoscopy. Abnormal fundus autofluorescence and/or near-infrared reflectance signals corresponded to accumulation of material located within the outer retina or in the Bruch membrane-retinal pigment epithelium (RPE) complex on spectral domain optical coherence tomography. Follow-up examinations during a 40-month period revealed progressive development of RPE atrophy in areas of pattern dystrophy-like changes. CONCLUSION: DFO retinopathy included a variety of pattern dystrophy-like changes or minimal changes affecting the RPE-Bruch membrane-photoreceptor complex. Multimodal imaging demonstrated that fundus changes were more diverse and widespread than expected from ophthalmoscopy. Consistently with previous histologic description of DFO retinopathy, multimodal imaging confirmed that photoreceptor outer-derived retinoids, various fluorophores, and RPE displacement or clumping are involved in DFO retinopathy, finally leading to frank RPE atrophy in most cases of pattern dystrophy-like changes.

Choroidal abnormalities detected by near-infrared reflectance imaging as a new diagnostic criterion for neurofibromatosis 1.

OBJECTIVE: To investigate in a large sample of consecutive patients with neurofibromatosis type 1 (NF1) the possibility of including the presence of choroidal abnormalities detected by near-infrared reflectance (NIR) as a new diagnostic criterion for NF1. DESIGN: Cross-sectional evaluation of a diagnostic test. PARTICIPANTS AND CONTROLS: Ninety-five consecutive adult and pediatric patients (190 eyes) with NF1, diagnosed based on the National Institutes of Health (NIH) criteria. Controls included 100 healthy age- and gender-matched control subjects. METHODS: Confocal scanning laser ophthalmoscopy was performed for each subject, investigating the presence and the number of choroidal abnormalities. MAIN OUTCOME MEASURES: Sensitivity, specificity, and diagnostic accuracy for the different cutoff values of the criterion choroidal nodules detected by NIR compared with the NIH criteria. RESULTS: Choroidal nodules detected by NIR imaging were present in 79 (82%) of 95 of the NF1 patients, including 15 (71%) of the 21 NF1 pediatric patients. Similar abnormalities were present in 7 (7%) of 100 healthy subjects, including 2 (8%) of the 25 healthy pediatric subjects. The highest accuracy was obtained at the cutoff value of 1.5 choroidal nodules detected by NIR imagery. Sensitivity and specificity of the examination at the optimal cutoff point were 83% and 96%, respectively. Diagnostic accuracy was 90% in the overall population and 83% in the pediatric population. Both of these values were in line with the most common NIH diagnostic criteria. CONCLUSIONS: Choroidal abnormalities appearing as bright patchy nodules detected by NIR imaging frequently occurred in NF1 patients. The present study shows that NIR examination to detect choroidal involvement should be considered as a new diagnostic criterion for NF1.

Abnormal fundus autofluorescence results of patients in long-term treatment with deferoxamine.

PURPOSE: To describe and classify patterns of abnormal fundus autofluorescence (FAF) of patients with ß-thalassemia receiving long-term treatment with deferoxamine (DFO). DESIGN: Prospective, cross-sectional, case-control study. PARTICIPANTS: A total of 197 consecutive patients with ß-thalassemia major or intermedia with at least 10 years of treatment with DFO were recruited in a tertiary referral center in Milan, Italy, and were investigated. Seventy-nine thalassemic patients without a history of chelation therapy were included as a control group. METHODS: All of the patients were investigated using best-corrected visual acuity (BCVA), fundus photography, and FAF imaging by confocal scanning laser ophthalmoscopy (cSLO) and were compared with the control group. MAIN OUTCOME MEASURES: Identification of abnormal FAF patterns in thalassemic patients treated with long-term DFO and their progression and relationship with visual function. RESULTS: Abnormal FAF not related to other diseases was observed in 18 of the 197 patients (9%) and was classified into 4 phenotypic patterns: minimal change, focal, patchy, and speckled. The abnormal increased or decreased FAF was bilateral in all the cases, and only in some cases did it correspond to funduscopically visible alterations. There were no FAF abnormalities in the control group. During the follow-up, progressive FAF changes related to retinal pigment epithelium (RPE) damage occurred in the patchy pattern, associated with decreasing BCVA. Patients with speckled and focal patterns showed limited or no changes in FAF during the follow-up. No changes in FAF were found in patients with a minimal change pattern. No treated patient with a normal baseline examination demonstrated FAF changes. Patients with patterns other than the minimal change showed significant BCVA deterioration (P<0.001). CONCLUSIONS: Various phenotypic patterns of abnormal FAF can be identified with cSLO imaging. Fundus autofluorescence is a helpful, fast, and noninvasive tool for monitoring the status of the macula in patients at risk of DFO toxicity. It may be useful in the decision to discontinue or switch the therapy in cases of particular high risk for disease progression. The progressive alteration of the RPE suggests an important role of pathologic RPE changes in the evolution of visual loss during long-term treatment with DFO.

OCT Analysis of Retinal Pigment Epithelium in Myopic Choroidal Neovascularization: Correlation Analysis with Different Treatments.

Objective: The objective of this study was to analyze the status of the retinal pigment epithelium (RPE) by means of the spectral domain optical coherence tomography (SD-OCT) overlying the myopic neovascular lesions in the involutive phase, looking for any correlations between the status of the RPE and the size of the lesions and the type and duration of the treatment. Methods: SD-OCT examinations of 83 consecutive patients with myopic choroidal neovascularization (CNV) were reviewed and divided into two groups: group A, patients with CNV characterized by uniformity of the overlying RPE, and group B, patients with CNV characterized by non-uniformity of the overlying RPE. Results: The median lesion area, major diameter, and minimum diameter were, respectively, 0.42 mm2 (0.30−1.01 mm2), 0.76 mm2 (0.54−1.28 mm2), and 0.47 mm2 (0.63−0.77 mm2) in group A, and 1.60 mm2 (0.72−2.67 mm2), 1.76 mm2 (1.13−2.23 mm2), and 0.98 mm2 (0.65−1.33 mm2) in group B. These values were lower in group A than in group B (p < 0.001). The number of treatments with a period free of disease recurrence for at least 6 months was greater (p < 0.010) in group B (6.54 ± 2.82) than in group A (3.67 ± 2.08), and treatments include intravitreal anti-vascular endothelial growth factor injection, photodynamic therapy, or both. Conclusions: Our results showed that the size of myopic neovascular lesion influences the development of a uniform RPE above the lesion and therefore the disease prognosis. The presence of uniform RPE was found to be extremely important in the follow-up of patients with myopic CNV, as it influences the duration of the disease and the number of treatments required.

The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes.

PURPOSE: Subthreshold micropulse laser (SMPL) has been increasingly used for the treatment of different retinal and choroidal macular disorders. However, the exact mechanisms of action have not yet been clearly defined. Therefore, we aimed to examine the role of SMPL treatment in the modulation of oxidant/antioxidant systems, apoptosis and autophagy in the mice eyes. METHODS: A specific laser contact lens for retina was positioned on the cornea of 40 mice (20 young and 20 old) in order to focus the laser on the eye fundus for SMPL treatment. Within 6 months, 20 animals received one treatment only, whereas the others were treated three times. Eye specimens underwent histological analysis and were used for thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) quantification, as well as for the superoxide dismutase 1 (SOD1) and the selenoprotein thioredoxin reductase 1 (TrxR1) expression evaluation. Western blot was performed for nitric oxide synthase (NOS) subtypes detection and to examine changes in apoptotic/autophagy proteins expression. RESULTS: SMPL treatment reduced TBARS and increased GSH and SOD1 in the mice eyes. It also reduced cytochrome c, caspase 3 expression and activity and cleaved caspase 9, and increased Beclin 1, p62 and LC3ß. The effects were more relevant in the elderly animals. CONCLUSION: Our results showed that SMPL therapy restored the oxidant/antioxidant balance within retinal layers and modulated programmed forms of cell death. Further studies may confirm these data and could evaluate their relevance in clinical practice.

Swept-source optical coherence tomography and optical coherence tomography angiography in acquired toxoplasmic chorioretinitis: a case report.

PURPOSE: To describe swept-source optical coherence tomography and optical coherence tomography angiography retinal changes in a case of acute toxoplasmic chorioretinitis both at the time of diagnosis and after healing. CASE PRESENTATION: A 57-year-old white woman suffering from acquired toxoplasmic chorioretinitis underwent swept-source optical coherence tomography and optical coherence tomography angiography both at the time of diagnosis and after healing. In the acute phase of the disease, swept-source optical coherence tomography clearly showed retinal and choroidal involvement in the superficial retina and in the choroidal swelling. Optical coherence tomography angiography showed a complete loss of deep and superficial capillary networks and of choroidal vessels in the area of the inflammation. After healing, swept-source optical coherence tomography showed a retinal thinning of the area involved, with a subversion of retinal layers and no visible change at the choroid level. On the other hand, optical coherence tomography angiography showed the persistence of a vascular occlusion at the retina and choroid level. CONCLUSION: This is the first case in the optical coherence tomography angiography literature that shows the imaging of toxoplasmic chorioretinal lesions. This case confirms the involvement of the retina and choroid in toxoplasmic uveitis and the disruptive potential of such inflammation. The optical coherence tomography angiography performed after healing showed a persistent ablation of the retina, choriocapillaris, and choroidal vessels. The non-invasive optical coherence tomography angiography imaging technique may have diagnostic and prognostic value in regard to toxoplasmic uveitis.

Purtscher-like Retinopathy in Septicemic Disseminated Intravascular Coagulation Associated with Nephrotic Syndrome.

PURPOSE: To describe a case of severe Purtscher-like retinopathy during an episode of septicemic diffused intravascular coagulation (DIC) in a child with severe nephrotic syndrome. METHODS: Case report. RESULTS: A 5-year-old girl with a history of steroid-sensitive nephrotic syndrome was admitted for worsening symptoms of the systemic disease. Laboratory studies revealed evidence of DIC during an episode of septicemia. Ten days later, she had a sudden and severe bilateral visual loss. Her visual acuity was hand motion in either eye. Fundus examination showed ischemic retinal whitening and retinal hemorrhages. Fluorescein angiography revealed obstruction of arterioles and venules at the posterior pole. Three weeks later, ischemic retinal blanching and hemorrhages resolved in both eyes; visual acuity improved to 20/250 and 20/200 in right and left eye, respectively. No further functional improvement was noted after 3 months, due to diffuse thinning of the inner retina architecture as shown by optical coherence tomography. CONCLUSIONS: Purtscher-like retinopathy can occur in patients with septicemic DIC and nephrotic syndrome.