Yoreh Barak

Spectral Domain Optical Coherence Tomography in the Diagnosis and Management of Vitreoretinal Interface Pathologies

The introduction of spectral domain optical coherence tomography (SD-OCT) has enhanced Vitreoretinal Interface (VRI) imaging considerably and facilitated the diagnosis, followup, prognosis determination, and management of VRI-associated pathologies. HR-OCT became a common practical tool seen in almost every ophthalmology practice. Knowledge of SD-OCT image interpretation and recognition of pathologies are required for all ophthalmologists. This paper methodically reviews the normal aging process of the VRI and discusses several commonly encountered VRI pathologies. The role of SD-OCT imaging in VRI-associated disorders such as posterior vitreous detachment, vitreomacular traction syndrome, idiopathic epiretinal membranes, lamellar holes, pseudoholes, and full thickness macular holes is portrayed. Future perspectives of new OCT technologies based on SD-OCT are discussed.

Mathematical Analysis of Specific Anatomic Foveal Configurations Predisposing to the Formation of Macular Holes

PURPOSE To mathematically analyze and to clinically describe specific anatomic foveal configurations predisposing to the formation of macular holes in comparison with normal foveal anatomy. METHODS In a retrospective observational case-control series, a total of 3882 optical coherence tomography (OCT) foveal thickness maps were analyzed; 96 foveal maps were identified before the formation of macular holes. Maps were analyzed using several anatomic measurements including: retinal thickness, foveal slope, and length of foveal depression. The mathematical analog of the foveal configuration was analyzed using automated symbolic regression software and the equation to describe the mathematical relationship in a 0.083 fit was derived for premacular hole foveas compared with normal age-matched foveas. RESULTS Premacular hole anatomic configuration was found to be significantly different from normal foveal anatomy for maximal slope (P < 0.05) and for central length of foveal depression (P < 0.05). The mathematical regression function followed a first-order cosine curve of level 12 complexity for normal fovea compared with a complex sine curve of level 30 complexity function for premacular hole fovea. Normal foveas had higher symmetry (0.86 ± 0.1, P = 0.03) along the midline, whereas premacular hole foveas had steeper maximal slopes (40 ± 18°, P = 0.01); 75% of these patients had similar foveal configuration in the fellow eye and 50% developed bilateral macular holes. CONCLUSIONS Premacular hole foveal configurations are significantly different from normal foveal configurations. Suspicious macular configurations are easy to recognize on OCT scans and may allow early diagnosis, follow-up, and better management of macular hole-prone patients.

The past, present, and future of exudative age-related macular degeneration treatment.

Treatment of exudative age-related macular degeneration has been revolutionized within the last 6 years with the introduction of vascular endothelial growth factor neutralizing agents. Previously popular “destructive treatments,” such as laser photocoagulation and photodynamic treatment have either been abandoned or used as an adjunct to pharmacotherapy. Despite the increase in vision after antivascular endothelial growth factor (VEGF) agents, they require repetitive and costly intravitreal injections that also carry the inherit risks of infection, retinal tears, and detachment. Several new and more potent VEGF inhibitors are at different stages of development. The goal of evolving pharmacotherapy is to preserve the therapeutic effect while reducing or eliminating the discomfort of intravitreal drug delivery, as well as identify new therapeutic targets. Complement inhibitors, immunomodulators, integrin inhibitors are a few of the new class of drugs that are expected to be in our armamentarium soon. Current medications act to decrease leakage through abnormal subretinal choroidal vasculature and promote involution. However, these medications are only effective in treating the active stage of the choroidal neovascular membrane. Restoration of vision of a large number of patients with involuted choroidal neovascular membranes is warranted. For this purpose, tissue engineering techniques have been employed to reconstruct the subretinal anatomy. Discovery of biomarkers, pharmacogenetics, and very specific targeting holds the promise of increased potency and safety in the future.

UNTREATED OBSTRUCTIVE SLEEP APNEA HINDERS RESPONSE TO BEVACIZUMAB IN AGE-RELATED MACULAR DEGENERATION.

Purpose: To compare functional and anatomical responses to intravitreal bevacizumab in patients with exudative age-related macular degeneration (AMD) between two groups of patients with obstructive sleep apnea (OSA) with and without treatment with continuous positive airway pressure therapy. Methods: Patients with OSA were categorized into 2 groups: 18 untreated and 20 treated with continuous positive airway pressure therapy. All patients had exudative AMD and received treatment with intravitreal bevacizumab. Central retinal thickness was plotted against time to assess anatomical response. Logarithm of the minimum angle of resolution visual acuity changes determined functional effect. Total number of intravitreal injections administered was assessed. Results: Treated OSA group received 8 ± 7 total injections; untreated OSA group received 16 ± 4 injections (P < 0.05). Treated OSA group achieved statistically significant better visual acuity (logarithm of the minimum angle of resolution, 0.3 ± 0.24, 20/40), as opposed to the untreated group (logarithm of the minimum angle of resolution, 0.7 ± 0.41; P < 0.05). Central retinal thickness improved in the treated OSA group compared with the untreated group: 358 ± 95 &mgr;m to 254 ± 45 &mgr;m and 350 ± 75 &mgr;m to 322 ± 105 &mgr;m, respectively (P < 0.05, 20/100). Conclusion: Untreated OSA hinders the response of exudative AMD to intravitreal bevacizumab. Treatment of OSA with continuous positive airway pressure therapy yields a subsequent anatomical response and functional improvement while requiring significantly less injections. Identifying and treating underlying OSA earlier in patients with exudative AMD may yield better functional outcomes.

Sealing Effect of External Diathermy on Leaking Sclerotomies After Small-Gauge Vitrectomy: A Clinicopathological Report

Sealing Effect of External Diathermy on Leaking Sclerotomies After Small-Gauge Vitrectomy: A Clinicopathological Report Small-gauge vitrectomy has surged in popularity in recent years and has become a widespread alternative to traditional techniques. Eighty-five percent of retinal surgeons now routinely use 25or 23-gauge systems for uncomplicated macular surgery compared with 22% in 2005.1 These small-gauge systems have advantages over largergauge systems, including shorter operative times, less tissue manipulation, decreased postoperative inflammation and pain, and quicker visual recovery.2 However, the sclerotomies are not routinely sutured in small-gauge vitrectomy, resulting in a unique set of potential postoperative complications, namely, wound leakage predisposing to postoperative hypotony, incomplete fill of tamponading agents, and possibly an increased risk of postoperative endophthalmitis. Applying external diathermy on a leaking sclerotomy is effective in sealing the surgical wound.3,4 The purpose of this clinicopathological report is to evaluate local histological and wound architecture changes in scleral wounds of varying sizes following the application of external diathermy.

Use of 25% sulfur hexafluoride gas mixture may minimize short-term postoperative hypotony in sutureless 25-gauge pars plana vitrectomy surgery

Background The purpose of this study was to compare postoperative intraocular pressures and percentage of vitreous cavity gas fill one day following 25-gauge pars plana vitrectomy with 20% versus 25% sulfur hexafluoride (SF6) gas fill. Methods This was a retrospective review of 187 consecutive cases of 25-gauge pars plana vitrectomy with complete fluid/gas exchange. The main outcome measures included percentage of gas fill of the vitreous cavity and intraocular pressure on postoperative day one. Results Fifty eyes underwent 25-gauge pars plana vitrectomy with 20% SF6 tamponade and 137 with 25% SF6 tamponade. On postoperative day one in the 20% SF6 group, there were five (10%) patients with hypotony (intraocular pressure ≤ 5 mmHg) and none in the 25% SF6 group. Mean intraocular pressure was 9 ± 2.5 mmHg and 16.8 ± 2.4 mmHg for the 20% SF6 and 25% SF6 groups, respectively (P < 0.01). None of the patients had postoperative intraocular pressure > 23 mmHg. Mean vitreous cavity gas fill on postoperative day one was 70.7% ± 10% in the 20% SF6 group and 89.5% ± 2.2% in the 25% SF6 group (P < 0.01). There was no difference in the number of phakic patients needing cataract surgery between the groups. Conclusion A slightly expansile concentration of 25% SF6 gas can be safely and beneficially used in 25-gauge vitrectomy surgery to increase the amount of gas fill in the vitreous cavity and prevent postoperative hypotony.

A Sema3C Mutant Resistant to Cleavage by Furin (FR-Sema3C) Inhibits Choroidal Neovascularization.

In age-related macular degeneration (AMD), abnormal sub retinal choroidal neovascularization (CNV) is a major cause of blindness. FR-sema3C is a point mutated form of semaphorin-3C that is resistant to cleavage by furin like pro-protein convertases (FPPC). We have found in previous work that FR-sema3C functions as an anti-angiogenic factor. In this study we investigated the possible use of FR-sema3C as an inhibitor of CNV. FR-sema3C inhibits VEGF as well as PDGF-BB signal transduction in endothelial cells and to less extent bFGF induced signal transduction using a mechanism that does not depend upon the binding of VEGF like the drugs that are currently the mainstay treatment for AMD. CNV was induced in eyes of C57 black mice by laser photocoagulation. Intravitreal injection of FR-Sema3C or aflibercept (VEGF-trap) was then used to inhibit CNV formation. Invading choroidal vessels were visualized a week later by injection of FITC-dextran into the circulation, followed by the measurement of the area of the invading blood vessels. Injection of 0.1 μg FR-Sema3C inhibited CNV by 55% (P<0.01) and was as effective as 5 μg aflibercept. FR-sema3C did not display any adverse effects on retinal function following its injection into eyes of healthy mice as assessed by optokinetic reflex (OKR) and Electro-retinogram (ERG) criteria. Furthermore, FR-sema3C did not induce apoptosis in the retina as determined by TUNEL nor was there any discernable structural damage to the retina as assessed by several immuno-histochemical criteria. Our results suggest that FR-sema3C could perhaps be used for the treatment of AMD, and that it may perhaps be of benefit to patients that do not respond well to current treatments relying on VEGF sequestering agents.

Rosai-dorfman disease diagnosed because of bilateral choroidal masses.

PURPOSE To describe a case of bilateral choroidal masses leading to the diagnosis of Rosai-Dorfman disease. METHOD Case report. Color photographs, fluorescein angiography, autofluorescence, indocyanine green angiography, and high-definition optical coherence tomography imaging of both eyes and computed tomography and biopsy of pelvis mass were performed. A 47-year-lady presented with unknown choroidal masses in both eyes. She had no visual complaints. Her medical history was noncontributory. RESULTS Workup included a computed tomography of the chest and abdomen that demonstrated soft tissue masses in the renal pelvis bilaterally. A core needle biopsy from the renal mass demonstrated numerous histiocytoid that were positive for CD163 and S100 protein. CONCLUSION Based on this spectrum of findings, the diagnosis of Rosai-Dorfman disease was made. To date, the patient has been followed-up for 3 years without medical intervention and without visual deterioration. Careful follow-up is a reasonable management if patients are asymptomatic.

Twenty-five-gauge vitrectomy for the removal of 5000 centistokes silicone oil.

Purpose: To compare the safety and efficacy of removing 5000 centistokes silicone oil between 20-gauge and 25-gauge vitrectomy technique. Methods: Prospective case series of 34 consecutive patients undergoing 5000 centistokes silicone oil removal using 20-gauge or 25-gauge cannulas. The main outcome measures were the safety and efficacy of silicone oil removal. The safety was evaluated by recording intraoperative and postoperative complication rates, including bleeding, recurrence of retinal detachment, hypotony, choroidal detachment, corneal edema, endophthalmitis, vitreous hemorrhage, conjunctival injection, and subconjunctival hemorrhage. The efficacy was judged by the ability to attain the complete removal of silicone oil and the total surgical time to complete the procedure. Results: Sixteen patients underwent 20-gauge vitrectomy for the removal of 5000 centistokes silicone oil between January 2008 and January 2010, and 18 patients underwent 25-gauge vitrectomy for the removal of 5000 centistokes silicone oil from January 2010 to August 2012. Silicone oil was successfully removed completely in all cases. Using 25-gauge vitrectomy to remove silicone oil was significantly more time efficient with the mean total surgical time of 25 ± 6 minutes compared with 42 ± 10 minutes in 20-gauge vitrectomy group (P < 0.05). There were no differences in the intraoperative or postoperative complication rates between the two groups. None of the patients developed postoperative recurrence of retinal detachment, hypotony, choroidal detachment, corneal edema, endophthalmitis, or vitreous hemorrhage. Conclusion: Twenty-five–gauge silicone oil removal is safe and effective. Surgical time is significantly reduced using sutureless 25-gauge sclerotomies. This may translate to cost reduction by decreasing time spent in the operating room.

Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study)

Purpose: To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. Methods: Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. Results: In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean (±standard deviation) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab. A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome. Conclusion: Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.