Computational Modeling of Ophthalmic Procedures: Computational Modeling of Ophthalmic Procedures.

PURPOSE: To explore how finite-element calculations can continue to contribute to diverse problems in ophthalmology and vision science, we describe our recent work on modeling the force on the peripheral retina in intravitreal injections and how that force increases with shorter, smaller gauge needles. We also present a calculation that determines the location and stress on a retinal pigment epithelial detachment during an intravitreal injection, the possibility that stress induced by the injection can lead to a tear of the retinal pigment epithelium. BACKGROUND: Advanced computational models can provide a critical insight into the underlying physics in many surgical procedures, which may not be intuitive. METHODS: The simulations were implemented using COMSOL Multiphysics. We compared the monkey retinal adhesive force of 18 Pa with the results of this study to quantify the maximum retinal stress that occurs during intravitreal injections. CONCLUSIONS: Currently used 30-gauge needles produce stress on the retina during intravitreal injections that is only slightly below the limit that can create retinal tears. As retina specialists attempt to use smaller needles, the risk of complications may increase. In addition, we find that during an intravitreal injection, the stress on the retina in a pigment epithelial detachment occurs at the edge of the detachment (found clinically), and the stress is sufficient to tear the retina. These findings may guide physicians in future clinical research. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

International multi-center study of iatrogenic retinal tears in pars plana vitrectomy.

AIM: To study and compare the effect of different surgical settings on the development of iatrogenic retinal tears (IRT) in conventional (20-gauge) and microincisional vitrectomy. METHODS: An international retrospective comparative study of 394 patients who had simple vitrectomy at three tertiary centers. Surgeries were performed by four retina surgeons using different viewing systems. Two groups of eyes were compared: microincisional vitrectomy (327 eyes) and conventional (67 eyes) vitrectomy. An iatrogenic tear was defined as the occurrence of one or more peripheral retinal tears during surgery or at any visit in the first 6wk postoperatively. RESULTS: Mean age was 67±12y and 55% were female. Iatrogenic tears occurred in 11/394 (2.8%) of eyes. The rate of tears was similar among different surgeons and viewing systems (P=0.93 and P=0.76, respectively). Surgical indication, preexisting pseudophakia/aphakia, induction of posterior vitreous detachment (PVD) during surgery, and the use triamcinolone acetonide didn't significantly affect the rate of tears (P>0.1 for all factors). A higher rate of tears was found in the conventional group compared to the microincisional group (respectively, 7.5%, 1.8%, P=0.02). CONCLUSION: The rate of IRT in vitrectomy is not significantly affected by surgical indication, preexisting PVD or pseudophakia, or use of triamcinolone or different viewing systems but is significantly higher in conventional vitrectomy. Microincisional platforms improve the safety of vitrectomy regardless of the viewing system used.

Sunlight and ultraviolet radiation-pertinent retinal implications and current management.

Unprotected and prolonged exposure to ultraviolet (UV) light from sunlight, lasers, and arc welding leads to outer retinal damage. The photoreceptors and retinal pigment epithelium located in the posterior pole are particularly susceptible to this radiation. Classically known as solar retinopathy, this disorder frequently affects young individuals who have clear lenses and a propensity toward observing solar eclipses. Various imaging techniques aid the clinician in diagnosis, even if patients cannot recall an exposure event. By far the most utilized technique is optical coherence tomography that, in tandem with fluorescein angiography, and fundus autofluorescence, is crucial in ruling out other conditions. Fortunately, the prognosis of acute UV retinopathy is favorable, as most cases fully recover; however, a significant percentage of patients suffer from chronic sequelae: reduced acuity and lifelong central/paracentral scotomas. Thus, education toward understanding UV exposure risks, coupled with either abstinence or proper eye protection, is critical in preventing macular damage. We outline the various etiologies responsible for UV-induced retinopathy, describe the limited treatments available, and provide recommendations to minimize the potential devastating ophthalmic consequences as our society increases its reliance on UV-emitting technology and further engages in solar eclipse viewing.

Osseous Metaplasia (Cataracta Ossea) of Lens Remnants in Chronic Uveitis-A Clinicopathologic Report.

PURPOSE: To describe clinically and pathologically the rare occurrence of calcification and osseous metaplasia in lens remnants in both eyes of a patient with pseudophakic chronic uveitis. METHODS: We performed 25-gauge pars plana vitrectomy, removal of dislocated intraocular lens (IOL), and secondary IOL fixation in the left eye. A similar procedure was performed in the right eye with 27-gauge pars plana vitrectomy. RESULTS: The postoperative visual acuities were 20/30 OD and 20/125 OS. Hematoxylin and eosin staining demonstrated an abundance of calcified tissue and rare osteoclasts in lacunae, compatible with osseous metaplasia (cataracta ossea). CONCLUSION: To our knowledge this is the first clinicopathologic report demonstrating cellular metaplasia that resulted in osseous transformation of the cortical lens remnants into bone in both eyes of a psuedophakic patient with chronic granulomatous pan uveitis of unknown etiology. The surgical technique described in the supplemental videos demonstrates an effective way of managing this complication.

COMPARISON OF 2D AND 3D VIDEO DISPLAYS FOR TEACHING VITREORETINAL SURGERY.

PURPOSE: To compare medical students' learning uptake and understanding of vitreoretinal surgeries by watching either 2D or 3D video recordings. METHODS: Three vitreoretinal procedures (tractional retinal detachment, exposed scleral buckle removal, and four-point scleral fixation of an intraocular lens [TSS]) were recorded simultaneously with a conventional recorder for two-dimensional viewing and a VERION 3D HD system using Sony HVO-1000MD for three-dimensional viewing. Two videos of each surgery, one 2D and the other 3D, were edited to have the same content side by side. One hundred UMass medical students randomly assigned to a 2D group or 3D, then watched corresponding videos on a MacBook. All groups wore BiAL Red-blue 3D glasses and were appropriately randomized. Students filled out questionnaires about surgical steps or anatomical relationships of the pathologies or tissues, and their answers were compared. RESULTS: There was no significant difference in comprehension between the two groups for the extraocular scleral buckle procedure. However, for the intraocular TSS and tractional retinal detachment videos, the 3D group performed better than 2D (P < 0.05) on anatomy comprehension questions. CONCLUSION: Three-dimensional videos may have value in teaching intraocular ophthalmic surgeries. Surgical procedure steps and basic ocular anatomy may have to be reviewed to ensure maximal teaching efficacy.

Association of Red Cell Distribution Width Values with Vision Potential in Retinal Vein Occlusion.

PURPOSE: To explore a possible association of red cell distribution width (RDW), a parameter that measures variation in red blood cell size or red blood cell volume and is an index of erythrocyte heterogeneity, with vision in patients with retinal vein occlusion (RVO). DESIGN: Cross-sectional study. PARTICIPANTS: Patients with either branch RVO (n = 70) or central RVO (n = 56) and gender-matched controls (n = 67) were included. METHODS: All participants underwent a comprehensive ophthalmologic examination, including fundus fluorescein angiography and macular OCT (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany). Exclusion criteria included RVO not confirmed by fluorescein angiography, history of malignancy, anemia, follow-up of less than 6 months, and unavailability of RDW value within 3 months of first presentation of RVO. Retinal vein occlusion patients were divided into 4 quartiles according to RDW value: quartile 1 (RDW ≤ 13.8%), quartile 2 (13.8% < RDW ≤ 14.8%), quartile 3 (14.8% < RDW ≤ 16.0%), and quartile 4 (RDW > 16.0%). Unpaired samples t tests, Pearson correlation tests, chi-square tests, analyses of variance, and multiple regression analyses were used for statistical evaluation. MAIN OUTCOME MEASURES: Red cell distribution width value and best-corrected visual acuity (BCVA). RESULTS: There was no significant difference in the demographics of participants in all 3 groups with respect to age, gender, and associated systemic diseases. Red cell distribution width was significantly higher in RVO patients (14.9±1.6 µm) compared with control participants (12.5±1.4 µm; P<0.0001). There was a statistically significant correlation between RDW value and both initial BCVA (r = 0.443; P<0.0001) and final BCVA (r = 0.379; P<0.0001) in RVO patients. Both initial and final BCVA were better in RDW quartiles 1 and 2 compared with RDW quartiles 3 and 4. CONCLUSIONS: Red cell distribution width was significantly higher in RVO patients compared with control participants. Furthermore, higher RDW value was associated with lower initial and final BCVA. Red cell distribution width merits further studies related to being a potential prognostic factor for vision in RVO patients.

Common and Rare Ocular Side-effects of the Dexamethasone Implant.

PURPOSE: Expanding indications for use, and overall increased use of the slow-release dexamethasone (DEX) implant yields an opportunity to study the reported ocular side-effects and adverse events associated with this drug. METHODS: A PubMed.gov (US National Library of Medicine, National Institutes of Health) review of literature for the search terms, "Ozurdex and complication," through December 2015. RESULTS: Ocular hypertension and cataract are the main long-term sequelae identified in large, randomized clinical trials. Case reports have emerged regarding implant migration, complications with implantation, infection, and posterior segment sequelae, including vitreomacular traction. CONCLUSION: DEX implant overall is well-tolerated and, with careful monitoring, can be a useful adjunct to treating macular edema associated with diabetes, retinal vein occlusion, and chronic uveitis.

VITREOMACULAR ADHESION EVOLUTION WITH AGE IN HEALTHY HUMAN EYES.

PURPOSE: To quantify the changes in vitreomacular interactions that occur with normal aging in normal eyes. METHODS: Spectral domain optical coherence tomography (SD-OCT, Spectralis; Heidelberg Engineering, Heidelberg, Germany) foveal scans of subjects with best corrected visual acuity better than 20/40 and no ocular pathology were included in the study. Each scan was analyzed to determine the status of vitreoretinal interface: complete vitreous adhesion, partial posterior vitreous detachment (PVD) with persistent vitreomacular adhesion (VMA), or complete PVD. Area of VMA was delineated using the Spectralis drawing tool and calculated in mm for each scan. Subjects, aged 10 years to 97 years, were divided into 9 age groups according to decade of life. RESULTS: Five hundred and sixty-six SD-OCT scans were analyzed. Area of VMA (mm) decreased sigmoidally (R = 0.99) with each decade of life. With aging, percentage of PVD increased while percentage of complete adhesion decreased. Males were found to have significantly larger area of VMA (mm) compared with females in the fifth through eighth decades of life, P < 0.05. CONCLUSION: Vitreomacular interface interactions throughout life are age and gender dependent. This adds to our current understanding of the normal aging process undergone by the vitreous, thereby providing assistance in the clinical differentiation between normal and pathologic vitreomacular interactions.

DIABETES ALTERS THE MAGNITUDE OF VITREOMACULAR ADHESION.

PURPOSE: To quantify the changes in vitreomacular interactions that occur with aging in diabetic eyes in comparison with age-matched control eyes. METHODS: Spectral-domain optical coherence tomography (Spectralis; Heidelberg Engineering) foveal scans of diabetic patients, without evidence of cystoid macular edema, were included. Twenty-five raster foveal scans were performed on every subject. Area of vitreomacular adhesion was delineated using the Spectralis drawing tool and calculated in square millimeter. Data collected included gender, race, best-corrected visual acuity, and posterior vitreous detachment status. Subjects were divided into age groups according to decade of life. RESULTS: Spectral-domain optical coherence tomography scans from 141 diabetic patients were analyzed. Area of vitreomacular adhesion (mm) showed a hyperbolic decline in diabetic patients (35.5 ± 0, 35.0 ± 3, 34.0 ± 3, 33.9 ± 5, 33.7 ± 6, 29.0 ± 11, 23 ± 15, 13 ± 15). With aging, incidence of posterior vitreous detachment increased and incidence of complete attachment decreased. CONCLUSION: Diabetes affects the magnitude of attachment of the vitreous gel to the macula that results in stronger and longer lasting attachment of the gel throughout life. Gender differences were not noticed in diabetic patients, suggesting that vitreomacular adhesion remains robust in both genders in diabetes despite aging.

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.

A SEMA3E mutant resistant to cleavage by furins (UNCL-SEMA3E) inhibits choroidal neovascularization.

Abnormal subretinal choroidal neovascularization (CNV) is a major cause of blindness in exudative age-related macular degeneration (AMD). Current anti-angiogenic treatments by VEGF sequestering agents have been successful, but a significant proportion of patients do not respond well to these treatments, and the response of others diminishes over time, suggesting that additional anti-angiogenic agents that function by separate mechanisms may be of use to such patients. We have previously found that a point mutated form of semaphorin-3E resistant to cleavage by furin like pro-protein convertases (UNCL-Sema3E) displays potent anti-angiogenic properties. We therefore determined if UNCL-Sema3E has potential as an inhibitor of CNV formation. We chose to study UNCL-Sema3E rather than wild type sema3E because unlike full length sema3E, the major p61-Sema3E peptide that is produced by cleavage of sema3E with furin like pro-protein convertases activates signal transduction mediated by the ErbB2 receptor and can promote tumor metastasis in addition to its anti-angiogenic activity. UNCL-Sema3E inhibited efficiently vascular endothelial growth factor-A (VEGF), platelet derived growth factor (PDGF) and basic fibroblast growth factor (bFGF) signaling in human umbilical vein derived endothelial cells (HUVEC) and to a lesser extent hepatocyte growth factor (HGF) signal transduction. CNV that was induced in the eyes of C57 black mice by laser photocoagulation was inhibited by 65% (P < 0.01) following a single bolus intra-vitreal injection of 5 µg UNCL-Sema3E. This inhibitory effect was similar to the inhibition produced by a single bolus intra-vitreal injection of 5 µg aflibercept. A similar inhibition of CNV was observed following the injection of UNCL-Sema3E into the eyes of Long-Evans rats. However, a higher dose of UNCL-Sema3E (125 µg), partially due to the larger volume of the vitreous cavity of rats, was required to achieve maximal inhibition of CNV. Injection of UNCL-Sema3E into eyes of healthy mice did not have any adverse effect on retinal function as assessed by optic kinetic reflex (OKR) or by electroretinogram (ERG) assays nor did UNCL-Sema3E injection affect the structure of the retina as determined using histology. To conclude, our results suggest that UNCL-Sema3E may be useful for the treatment of exudative AMD, which does not respond well to conventional anti-VEGF therapy.

POSTCATARACT ENDOPHTHALMITIS TREATED WITH SMALL GAUGE VITRECTOMY.

PURPOSE: To discuss the use of minimally invasive, small gauge vitrectomy for acute postcataract endophthalmitis in patients with better than light-perception vision. PATIENT: 71-year-old man presented with redness, pain, and decreased vision of his left eye 11 days after cataract extraction. His visual acuity was counting fingers at 1 foot and slit-lamp examination revealed severe conjunctival injection, corneal edema, and hypopyon. The clinical impression was of acute postcataract endophthalmitis. METHODS: Patient was taken for immediate vitrectomy with simultaneous vitreous tap for culture, PCR, and injection of intravitreal vancomycin and ceftazidime. RESULTS: Culture and PCR of vitreous sample were positive for Staphylococcus epidermidis. Vision improved to 20/20 1 month postoperatively with complete resolution of vitreous inflammation and retinal vasculitis. CONCLUSION: In postcataract endophthalmitis with dense vitritis and diffuse retinal vasculitis, immediate, 25-gauge vitrectomy may result in return of baseline visual acuity.

Delivery of steroids into the eye for the treatment of macular edema.

INTRODUCTION: Steroids have been in extensive use in ophthalmology since their discovery in 1948. Steroids are effective for the treatment of macular edema and may be delivered into the eye either topically, systemically, subconjunctivally, sub-Tenon, intravitreally and through injectable sustained release devices. Various steroid formulations and devices are commercially available. Each carries advantages and disadvantages, which requires the ophthalmologist to exercise careful medical judgment upon treatment selection. AREAS COVERED: This article focuses in steroid delivery into the eye for the treatment of macular edema, and reviews the current and future treatment options, summarizing their clinical efficacy and possible adverse effects. EXPERT OPINION: Steroids have an important role in the treatment of macular edema, regardless of its cause. Steroids are efficacious, low-cost, and much clinical experience has been accumulated regarding their use over the years. Prolonged systemic steroid use may be associated with severe systemic and local side effects, directly proportional to dosage and time. Intravitreal delivery of steroids has gained popularity as the medication is administered close to the target tissue, significantly reducing the possibility of systemic adverse effects. The biggest problem associated with intravitreal steroids still remains unacceptably high risk of glaucoma and cataract formation. Various controlled-release intravitreal delivery devices are currently commercially available, and more are in the pipeline. While they still carry the risk of local side effects, they are efficacious and can control macular edema for months and years after a single administration.

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 µm to 254 ± 45 µm and 350 ± 75 µm to 322 ± 105 µm, 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.

A Comparison of Immediate and Delayed Vitrectomy for the Management of Vitreous Hemorrhage due to Proliferative Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To compare immediate and delayed vitrectomy for the management of vitreous hemorrhage (VH) due to proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: Retrospective review of 134 eyes receiving vitrectomy for non-clearing, PDR-associated VH. Primary outcome was area under the vision curve (AUC) in patients receiving immediate (< 30 days) versus delayed (> 30 days) vitrectomy with endolaser. RESULTS: Forty-six eyes were included, with 17 undergoing immediate (< 30 days) vitrectomy with endolaser and 29 undergoing delayed (> 30 days) vitrectomy with endolaser. Time to vitrectomy was 14.8 days ± 8.26 days compared to 629.6 days ± 894.9 days in the immediate and delayed groups, respectively. AUC was significantly greater for patients undergoing delayed versus immediate vitrectomy (276.1 ± 0.601 logMAR*time versus 165.7 ± 0.761 logMAR*time; P < .0001). There was no difference in AUC postoperatively for delayed versus immediate surgery. Both groups required significantly less postoperative panretinal photocoagulation (P < .05). Preoperative and final visual acuities were equivalent (immediate: 1.86 ± 0.99 and 0.35 ± 0.25; P = .002; delayed: 1.71 ± 1.05 and 0.31 ± 0.34; P < .0001). CONCLUSIONS: Immediate vitrectomy with endolaser for PDR-associated VH (< 30 days) decreases time spent with vision loss and the need for adjunctive PRP. Modern vitrectomy is safe and may be considered earlier in VH management.