Shulamit Schwartz

Central corneal thickness measurement with the Pentacam Scheimpflug system, optical low-coherence reflectometry pachymeter, and ultrasound pachymetry

PURPOSE: To assess the intraoperator repeatability and interoperator reproducibility of central corneal thickness measurements by the Pentacam Scheimpflug imaging system (Oculus) and the optical low‐coherence reflectometer (OLCR) pachymeter (Haag‐Streit) and to compare them with those of ultrasound (US) pachymetry. SETTING: Assaf Harofe Medical Center Ophthalmology Outpatient Clinic, Zerifin, Israel. METHODS: Repeatability was determined from 10 successive measurements in each of 4 healthy patients. Reproducibility for the Pentacam Scheimpflug system was determined from measurements by 2 operators in each of 24 patients; in these 24 patients, central corneal thickness measurements were compared between the Pentacam and US pachymetry. For the OLCR pachymeter, reproducibility was determined from measurements by 2 operators in each of 16 patients, in whom central corneal thickness was also measured with the Pentacam. RESULTS: Mean coefficient of repeatability was 0.84% for the Pentacam Scheimpflug system and 0.33% for the OLCR pachymeter. For the Pentacam, the coefficient of interoperator reproducibility was 1.10% and the 95% limits of agreement were −10.2 μm to +11.9 μm. Mean difference between Pentacam and US was 6.09 μm. For the OLCR pachymeter, the coefficient of interoperator reproducibility was 0.59% and the 95% limits of agreement were −5.4 μm to +7.0 μm. Mean difference between central corneal thickness values obtained with the OLCR pachymeter and Pentacam Scheimpflug system was 1.7 μm. CONCLUSIONS: Objective, noncontact measurement of central corneal thickness with the Pentacam Scheimpflug system and OLCR pachymeter was convenient and yielded excellent intraoperator repeatability and interoperator reproducibility. Central corneal thickness values obtained with the Pentacam were similar to those obtained with both the OLCR pachymeter and an US pachymeter. Further research is needed to corroborate whether central corneal thickness measurements by the Pentacam and OLCR devices can be used interchangeably and are more clinically useful than US pachymetry.

Long-term effect of antiangiogenic therapy for retinopathy of prematurity up to 5 years of follow-up.

Purpose: To evaluate ocular function and systemic development in premature infants treated with intravitreal bevacizumab injections for retinopathy of prematurity over a period of 5 years. Methods: A prospective, interventional, noncomparative case study. The primary outcome measure was visual acuity. The secondary outcomes were structural assessment, other ocular functional measurements, and developmental state. Results: Eighteen eyes of 13 consecutive patients were divided into 3 groups: Group 1, Stage 4 unresponsive to previous conventional treatment (n = 4); Group 2, in which conventional treatment was difficult or impossible because of inadequate visualization of the retina (n = 5); and Group 3, newly diagnosed high-risk prethreshold or threshold retinopathy of prematurity (n = 9). All patients showed initial regression of neovascularization. One patient was diagnosed with recurrence of neovascularization and was treated with intravitreal bevacizumab. Visual acuity was preserved, and median vision was 20/25 (excluding 2 operated eyes). Twelve eyes developed mainly low myopia over the years, with an overall mean value of 3.2 diopters. Electroretinograph was normal in 4 eyes that had no previous detachment. One patient showed delay in growth and neurodevelopment, whereas all the others were within the normal range. Conclusion: Five years of follow-up in a small series suggest that intravitreal bevacizumab for retinopathy of prematurity results in apparently preserved ocular function and systemic development.

Constitutive Expression of HIF‐1α and HIF‐2α in Bone Marrow Stromal Cells Differentially Promotes Their Proangiogenic Properties

Bone marrow stromal cells (BMSCs) contain progenitors capable of participating in postnatal angiogenesis. Hypoxia‐inducible factors (HIFs) mediate endothelial activation by driving the expression of multiple angiogenic factors. We explored the potential of HIF‐1α and HIF‐2α modification in BMSCs, as a tool to improve cell‐based angiogenic therapy. BMSCs were retrovirally transduced to express stable forms of HIF‐1α and HIF‐2α. HIF‐1α and, to a greater extent, HIF‐2α overexpression promoted differentiation of BMSCs to the endothelial lineage, evident by CD31 and Tie‐2 expression and improved adhesive properties. Whereas chemotaxis toward stromal‐derived factor 1 was higher in both HIF‐α‐expressing BMSCs, enhanced migration toward vascular endothelial growth factor was found only following overexpression of HIF‐2α, supported by a robust expression of its receptor, Flk‐1. HIF‐α expression was associated with upregulation of angiogenic proteins and improved tube formation. Cytokine arrays of endothelial cells stimulated by medium collected from HIF‐α‐expressing BMSCs revealed further angiogenic activation and improved adhesive capacity. Eventually, delivery of HIF‐2α‐transduced BMSCs induced a more robust angiogenic response, compared with sham‐transduced or HIF‐1α‐transduced BMSCs in the corneal micropocket angiogenesis model. Our results support the use of HIF‐α genes, particularly HIF‐2α, to augment the efficacy of future cell‐based therapy.

Drug Modification of Angiogenesis in a Rat Cornea Model

PURPOSEnTo evaluate the influence of some widely used antiglaucoma agents on angiogenesis in a novel rat cornea model.nnnMETHODSnAngiogenesis was induced in 32 rats by slow-release polymer pellets containing basic fibroblast growth factor (bFGF) placed in a corneal micropocket. Angiogenesis was later measured and compared in groups of rats given one of four antiglaucoma drug therapies and one control group. The drugs were commercially available preparations of prostaglandins, beta-blockers, alpha-2 agonists, and carbonic anhydrase inhibitors given for 7 days in a manner similar to that used in humans. Growth was measured by calculating the maximum linear vessel growth divided by pellet-limbus distance.nnnRESULTSnBiomicroscopic observation disclosed that all tested animals showed an induction of neovascular reactions in their corneal stroma. The growth index results for the control, latanoprost, dorzolamide, brimonidine, and timolol malate groups were 1.65 +/- 0.16, 1.98 +/- 0.18, 1.85 +/- 0.19, 2.03 +/- 0.38, and 1.65 +/- 0.14, respectively, confirming the hypothesis that topically delivered antiglaucoma drugs modify the normal angiogenic response. Of them, the prostaglandins showed the most prominent angiogenic stimulatory effect (P = 0.03).nnnCONCLUSIONSnThis modified micropocket assay of corneal angiogenesis in rats demonstrated the stimulatory effect of several widely used topically delivered antiglaucoma medications on the angiogenic process. The results indicate that the selection of drugs for treating different ophthalmic diseases should take into account their influence on angiogenic processes.

Massive subretinal and subretinal pigment epithelial hemorrhage displacement with perfluorocarbon liquid using a two-step vitrectomy technique

PurposeThe purpose of this study was to evaluate the efficacy and visual outcome of massive submacular hemorrhage (SMH) displacement with a planned two-step pars plana vitrectomy (PPV) using tissue plasminogen activator (tPA) and perfluorocarbon liquid (PFCL) tamponade.MethodsA retrospective case series of patients with age related macular degeneration and SMH was used. All patients underwent a 23G PPV, subretinal tPA injection and a medium term PFCL tamponade. A second stage PPV for PFCL removal was performed 7-17 days later. The main outcome was the change in macular and sub-RPE thickness after 6 months. Secondary outcomes were visual acuity and complications.ResultsSeven patients (seven eyes) with mean age of 79.85 years were enrolled. The average SMH size was 17.5 disc area (range 4.5-33) with mean symptoms of a duration of 9.5 days (range: 2-21). SMH was successfully displaced in six eyes. Mean macular and sub-RPE thickness decreased from 1505μ to 711.3μ and 900 μ to 457μ, respectively. Visual acuity (VA) remained stable in five eyes. Complications included corneal edema and transient intraocular pressure elevation in three patients.ConclusionsSMH displacement using subretinal tPA injection and medium term PFCL tamponade is an effective alternative treatment option. In our experience, it can be safely performed, avoiding complications commonly attributed to other techniques.

Noninfectious Inflammatory Response following Intravitreal Bevacizumab Injections: Description of a Cluster of Cases in Two Centers and a Review of the Literature

Purpose: To report a cluster of high incidence of noninfectious inflammatory reaction shortly after bevacizumab injection. Methods: Data were collected from medical records of consecutive patients who underwent bevacizumab injections and presented with acute uveitis within 1–4 days. Results: All 7 patients were injected intravitreally with bevacizumab from different batches and presented with visual deterioration. One patient with anterior uveitis complained of pain. None had hypopyon. Three patients with vitritis underwent a vitreous tap with an intravitreal injection of vancomycin and ceftazidime for possible infectious endophthalmitis. All patients received intensive topical antibiotic drops and steroids, and the intraocular inflammation resolved completely within 1 month. Five patients continued to receive bevacizumab injections without recurrent episodes. Conclusions: Our series demonstrates an incidence of noninfectious inflammatory reaction shortly after bevacizumab injection that is higher than that reported in the literature. The cause is more likely the preparation process in the same compounding pharmacy.

Disorganization of Retinal Inner Layers as a Biomarker for Idiopathic Epiretinal Membrane After Macular Surgery—The DREAM Study

PURPOSEnEpiretinal membrane (ERM) can cause distortion and disorganization of all inner retinal layers. The purpose of our study was to evaluate the extent of disorganization of the retinal inner layers (DRIL) and to investigate its predictive value for visual outcome in cases of idiopathic ERM that were treated by pars plana vitrectomy (PPV) and ERM peeling.nnnDESIGNnMulticenter international retrospective case series.nnnMETHODSnIn 90 eyes from 90 patients with idiopathic ERM treated by PPV and membrane peeling with 12-month follow-up, optical coherence tomography (OCT) scans previous to surgery were evaluated for presence and severity of DRIL, central foveal subfield thickness (CST), maximal retinal thickness (MRT), presence of intraretinal cystoid changes and subretinal fluid, and integrity of the inner/outer segment layer and of the interdigitation zone. Best-corrected visual acuity (BCVA), CST, and MRT were recorded at baseline and at 3, 6, and 12xa0months after surgery. Correlations between baseline OCT measures (DRIL) and functional and visual outcome were analyzed. Main outcome measures are presence and severity of DRIL at baseline; anatomic and functional outcomes after 3, 6, and 12xa0months; and the correlation between DRIL and baseline characteristics and outcome measures.nnnRESULTSnPatients without and with mild DRIL had a significantly better baseline BCVA compared with patients with severe DRIL (0.61 ± 0.13, 0.56 ± 0.23, 0.73 ± 0.20 [logMAR], respectively). BCVA, CST, and MRT at baseline were statistically significantly correlated with DRIL severity (Pxa0= .003, P < .001, and P < .001, respectively). DRIL status before surgery showed a statistically significant interaction with change in BCVA, CST, and MRT over 12xa0months (P < .001 for all). Patients without and with mild DRIL gained a mean of 3 lines of vision after 12xa0months, in contrast to 1 line in patients with severe DRIL.nnnCONCLUSIONSnDRIL grading correlates with functional and anatomic measures in patients with idiopathic ERM and could serve as a biomarker to predict outcome after surgery. Patients with severe DRIL have limited benefits from surgery. This should be considered in the decision process whether to perform ERM peeling in this patient group.

INTERNAL ASPIRATION UNDER PERFLUOROCARBON LIQUID FOR THE MANAGEMENT OF LARGE MACULAR HOLES

Purpose: To report the outcomes of pars plana vitrectomy with internal aspiration under perfluorocarbon liquid for large macular holes (MH). Methods: Retrospective consecutive case series of patients with large (>400 µm) MH. All treated were with pars plana vitrectomy, internal limiting membrane peeling, internal fluid aspiration under perfluorocarbon liquid, and gas/oil tamponade. Outcomes included closure rate and visual acuity at 6 months. Results: Twenty eyes of 20 patients were included. Mean age of patients was 67.6 ± 7.3 years. Mean MH size was 609.4 ± 154.7 &mgr;m. Mean symptoms duration was 9.05 ± 7.3 months. Unfavorable prognostic factors included chronic MHs (≥4 months) in 15 eyes (75%), refractory MH in 6 eyes (30%), and poor initial visual acuity (⩽20/200 logarithm of minimal angle of resolution) in 18 eyes (90%). Gas tamponade was used in 18 eyes (90%). Nineteen MHs (95%) had closed after a single operation. Two (10.5%) had Type-II closure. Mean visual acuity improved significantly from 20/330 to 20/140 Snellen acuity (1.22 ± 0.31–0.85 ± 0.35 logarithm of minimal angle of resolution; P < 0.001). Fifteen eyes (75%) had visual acuity improvement of more than 0.2 logarithm of minimal angle of resolution. Thirteen eyes (65%) achieved visual acuity better than 20/200. Conclusion: Pars plana vitrectomy combined with internal fluid aspiration under perfluorocarbon liquid is an effective and safe surgical technique for the management of large MH. This innovative technique offers improved closure rates and visual acuity results.

Serum ischemia modified albumin and vascular endothelial growth factor levels following intravitreal bevacizumab injections

Purpose Previous reports have demonstrated that the serum levels of vascular endothelial growth factor (VEGF) are reduced after intravitreal injections of bevacizumab. This study aimed to determine the serum levels of ischemia-modified albumin (IMA), a marker of ischemia, and VEGF following intravitreal injections of bevacizumab. Methods This was a prospective study. Blood samples were drawn prior to injection and at 1, 7, and 30 days after injection. Results A total of 11 patients participated in this study. Mean serum IMA levels were lower than baseline during follow-up, with statistically significant differences compared to baseline levels at day 1 and day 30 (preinjection: 49.82 ± 15.28 ng/mL; 44.57 ± 12.01 ng/mL, p = 0.007, and 43.71 ± 13.82 ng/mL, p = 0.001, respectively). Mean serum VEGF levels were lower than baseline throughout the follow-up period (from 307.45 ± 273.45 pg/mL at baseline to 159.55 ± 120.68 pg/mL at day 30). Mean serum VEGF levels were significantly lower compared to baseline levels at day 1 and day 7 (147.09 ± 106.08 pg/mL, p = 0.014; 72.91 ± 50 pg/mL, p = 0.011, respectively). Conclusions In this study, mean serum IMA and VEGF levels were lower following intravitreal bevacizumab injections.

Inner Segment Ellipsoid Band and Cone Outer Segment Tips Changes Preceding Macular Hole Development in a Young Patient

Purpose. Pathophysiology of macular hole (MH) is not yet well defined but the advances of spectral domain optical coherence tomography (SD-OCT) give us access to further detailed imaging. We report a case with macular inner segment ellipsoid (ISe) band loss and cone outer segment tips (COST) line changes seen in SD-OCT preceding MH appearance in a young patient. Methods. 21-year-old woman presented with a partial central scotoma, metamorphopsia, and a 20/25 vision in her right eye. Past medical history was positive for laser assisted in situ keratomileusis (LASIK) surgery 7 months ago with no complications. Macular SD-OCT showed ISe band loss and COST line elevation. She was followed a month later with visual acuity deteriorating to 20/200 and a full thickness MH. Results. The patient underwent a pars plana vitrectomy with internal limiting membrane peeling. Her visual acuity 2 months later was 20/20. Conclusion. SD-OCT can identify preliminary changes, yet to be described, preceding MH formation. Our patient demonstrated ISe band loss and COST abnormalities on SD-OCT a month prior to MH development. SD-OCT should be considered in young patients with subtle visual symptoms and mild changes in visual acuity that are not readily explained by ophthalmological exam.