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.

EX VIVO MODEL FOR THE CHARACTERIZATION AND IDENTIFICATION OF DRYWALL INTRAOCULAR FOREIGN BODIES ON COMPUTED TOMOGRAPHY.

BACKGROUND: The study was inspired after the authors encountered a patient with a penetrating globe injury due to drywall, who had retained intraocular drywall foreign body. Computed tomography (CT) was read as normal in this patient. Open globe injury with drywall has never been reported previously in the literature and there are no previous studies describing its radiographic features. METHODS: The case report is described in detail elsewhere. This was an experimental study. An ex vivo model of 15 porcine eyes with 1 mm to 5 mm fragments of implanted drywall, 2 vitreous only samples with drywall and 3 control eyes were used. Eyes and vitreous samples were CT scanned on Days 0, 1, and 3 postimplantation. Computed ocular images were analyzed by masked observers. Size and radiodensity of intraocular drywall were measured using Hounsfield units (HUs) over time. RESULTS: Intraocular drywall was hyperdense on CT. All sizes studied were detectable on Day 0 of scanning. Mean intraocular drywall foreign body density was 171 ± 52 Hounsfield units (70-237) depending on fragment size. Intraocular drywall foreign body decreased in size whereas Hounsfield unit intensity increased over time. CONCLUSION: Drywall dissolves in the eye and becomes denser over time as air in the drywall is replaced by fluid. This study identified Hounsfield Units specific to intraocular drywall foreign body over time.

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.

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.

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.

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.

TISSUE PLASMINOGEN ACTIVATOR FOR SUBFOVEAL HEMORRHAGE DUE TO AGE-RELATED MACULAR DEGENERATION: Comparison of 3 Treatment Modalities.

PURPOSE: To analyze and compare the effects of three common treatment modalities for a thick subfoveal hemorrhage due to exudative age-related macular degeneration on final visual acuity and the size of the final subretinal scar. DESIGN: Retrospective case series. SETTING: Single-site, tertiary referral center. PATIENTS: Thirty-nine patients with exudative age-related macular degeneration and acute SMH greater than 250 µm. INTERVENTION: Patients received vitrectomy with a subretinal tissue plasminogen activator (tPA) injection, pneumatic displacement (PD) with intravitreal tPA, or PD without tPA within 2 weeks of presentation. MAIN OUTCOME MEASURE: Functional outcome was determined by Snellen visual acuity. Anatomical outcome was determined as the final disciform scar size. RESULTS: Treatment groups did not differ in age, sex, initial visual acuity, the initial area of the thick subfoveal hemorrhage, follow-up duration, lens status, duration of exudative age-related macular degeneration, previous intravitreal bevacizumab injections, or time from last given injection to the acute thick subfoveal hemorrhage. Final visual acuity improved significantly in both the vitrectomy and subretinal tPA injection group (P < 0.001), and the intravitreal tPA injection group (P = 0.002) but not with PD alone. Patients treated with subretinal tPA achieved 40% ± 54% reduction in final scar area, in contrast to 27% ± 35% decrease in patients treated with intravitreal tPA (P = 0.001). CONCLUSION: Treatment with tPA improves the functional and anatomical outcomes in patients with thick subfoveal hemorrhage due to subfoveal choroidal neovascular membrane secondary to exudative age-related macular degeneration and was superior to PD without tPA. Vitrectomy with subretinal tPA injection reduced the final disciform scar compared with PD with or without intravitreal tPA.

EVOLUTION OF CONTROLLING DIABETIC RETINOPATHY: Changing Trends in the Management of Diabetic Macular Edema at a Single Institution Over the Past Decade.

PURPOSE: To report the evolution of treatment in managing diabetic macular edema (DME) in a "real world" clinical setting. METHODS: Retrospective observational case series of 1,862 patients treated for DME over the last decade. Change in selection of treatment modalities used for controlling DME, visual acuity, and degree of DME on optical coherence tomography were recorded. RESULTS: Over the past decade, there was a linear decrease in laser use, with exponential growth in the utilization of intravitreal injections. An increase in the frequency of clinic visits from 3 ± 2 visits per year to 9 ± 2 visits per year with significant visual and anatomical improvements was noted: mean improvement in visual acuity increased from 0.01 ± 0.1 logMAR units (which is equivalent to less than 1 Snellen line) to 0.3 ± 0.2 logMAR units (which is equivalent to 2 Snellen lines) (P < 0.05), mean decrease in retinal thickness changed from 58 ± 59 µm to 162 ± 91 µm (P < 0.05). CONCLUSION: An evolution in treatment strategy for controlling DME over the last decade was reflected by the replacement of focal laser therapy with intravitreal injections. This has produced significant improvements in visual and anatomical outcomes but has increased the frequency of office visits.

THE OMAR STUDY: Comparison of Ozurdex and Triamcinolone Acetonide for Refractory Cystoid Macular Edema in Retinal Vein Occlusion.

PURPOSE: To compare the risks and benefits of adding either intravitreal dexamethasone implant (DEX) or preservative-free triamcinolone acetonide (TA) to bevacizumab monotherapy in refractory cystoid macular edema due to retinal vein occlusion. METHODS: This is a multicenter, comparative, interventional, retrospective study that included 74 patients who were initially treated with intravitreal bevacizumab and later received either DEX or TA for the treatment of recalcitrant cystoid macular edema due to retinal vein occlusion. Main outcomes were best-corrected visual acuity, central macular thickness, cost of therapy, frequency of intravitreal injections, and side effects. RESULTS: Thirty-nine patients received TA and 35 patients received DEX injections. Groups were similar in age and gender distribution. Although the mean central macular thickness improved significantly for all groups (P < 0.0001), logMAR best-corrected visual acuity did not change significantly after steroid introduction (P = 0.06). Frequency of any intravitreal injection decreased significantly from 0.66 ± 0.18 to 0.26 ± 0.08 injections per month after initiation of steroids (P < 0.0001). This effect was greater in the DEX groups (P < 0.0001). Monthly cost decreased with TA but increased with DEX. CONCLUSION: Adding steroids improved anatomical outcome but did not affect final vision. Injection frequency decreased significantly after adding steroids, more so with DEX. There was no difference between TA and DEX regarding anatomical or functional outcomes or the incidence of side effects.

Mini-cognitive testing in patients with age-related macular degeneration.

PURPOSE: To compare Mini-Cognitive (Mini-Cog) Screening test results between patients with age-related macular degeneration (AMD) and age-matched controls. PARTICIPANTS: Two hundred and twenty-nine patients were included in the study. Patients were divided into 3 groups: 56 patients with exudative AMD, mean age of 76 ± 8 years; 82 patients with dry AMD, mean age of 77 ± 9 years; and 91 controls, mean age of 75 ± 8 years. METHODS: The Mini-Cog test, used to screen patients with early cognitive impairment, was introduced to the three groups of patients at the settings of an ophthalmology outpatient clinic. Test scores were compared between the groups. RESULTS: The mean for the Mini-Cog test scores was 3.5 (95% confidence interval, 3.15-3.85) for the dry AMD group, 3.95 (95% confidence interval, 3.51-4.39) for the exudative AMD group, and 4.63 (95% confidence interval, 4.45-4.80) for the control group. There was no statistically significant difference between the scores of AMD groups, however, both AMD groups received significantly lower scores than controls (P < 0.0001). CONCLUSION: Patients with age-related macular degeneration in this study demonstrated lower mean scores in the Mini-Cog test than age-matched controls. The Mini-Cog test may be easily applied at an office setting of ophthalmology outpatient clinics, and may help in the early diagnosis of cognitive impairment in the patients with AMD.

Poor responders to bevacizumab pharmacotherapy in age-related macular degeneration and in diabetic macular edema demonstrate increased risk for obstructive sleep apnea.

PURPOSE: To investigate the risk for obstructive sleep apnea (OSA) in patients with exudative age-related macular degeneration (AMD) or diabetic macular edema with poor response to anti-vascular endothelial growth factor therapy with bevacizumab (Avastin). METHODS: Age-related macular degeneration group was categorized into nonexudative, exudative, or poor response exudative. Diabetic macular edema group included patients with nonproliferative diabetic retinopathy and cystoid macular edema. Patients were categorized based on the number of intravitreal injections of bevacizumab received. Both groups were compared with age-matched controls. Patients completed a screening questionnaire to assess the risk for OSA, the main outcome measure. RESULTS: Of 103 patients with AMD, 56 (54.37%) had nonexudative AMD and 47 (45.63%) had exudative AMD, of which 14 (29.79%) had poor response exudative AMD and were at a significantly higher risk of OSA (P < 0.05). Of 30 diabetic macular edema patients with cystoid macular edema, 4 (19%) received 1 injection, 18 (81.82%) received 2 or more consecutive injections, and 16 (72.73%) received 3 or more consecutive injections. Risk for OSA increased significantly with increasing number of injections (P < 0.05). CONCLUSION: Patients with exudative AMD and diabetic macular edema with poor response to anti-vascular endothelial growth factor therapy have a significantly higher risk of OSA compared with age-matched controls and should be screened to assess the risk of OSA.

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.

Factors affecting patients' pain intensity during in office intravitreal injection procedure.

PURPOSE: To determine factors associated with patients' comfort during routine in-office intravitreal injection. METHODS: Sixty patients receiving intravitreal injections over 15 months for macular edema because of diabetes, age-related macular degeneration, or retinal vein occlusion who were randomized into 3 groups to receive 1 of 3 commonly used forms of anesthesia-TetraVisc, proparacaine HCl, or tetracaine HCl-before receiving intravitreal injection were studied. Fifteen minutes after injection, patients were asked to rate their pain from 0 (no pain/no distress) to 10 (agonizing pain/unbearable distress) using a Visual Analog Pain score survey. Self-reported pain scores were stratified by age, gender, diagnosis, injection number, substance injected, needle gauge, and visual acuity improvement. RESULTS: Intravitreal injection was associated with low pain scores. Patients receiving tetracaine reported a statistically significant lower pain score (3.05 ± 2.01) than patients receiving proparacaine (3.17 ± 2.18) or TetraVisc (3.3 9± 2.26; P < 0.01). Other important factors influencing pain score significantly (P < 0.01) included improved vision from previous injection, female sex, and age >65 years. Pain scores decreased with each consecutive injection. CONCLUSION: Pain associated with intravitreal injection is generally mild, and may be associated with epidemiologic and environmental factors.

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.