Systemic retinal biomarkers.

PURPOSE OF REVIEW: Systemic retinal biomarkers are biomarkers identified in the retina and related to evaluation and management of systemic disease. This review summarizes the background, categories and key findings from this body of research as well as potential applications to clinical care. RECENT FINDINGS: Potential systemic retinal biomarkers for cardiovascular disease, kidney disease and neurodegenerative disease were identified using regression analysis as well as more sophisticated image processing techniques. Deep learning techniques were used in a number of studies predicting diseases including anaemia and chronic kidney disease. A virtual coronary artery calcium score performed well against other competing traditional models of event prediction. SUMMARY: Systemic retinal biomarker research has progressed rapidly using regression studies with clearly identified biomarkers such as retinal microvascular patterns, as well as using deep learning models. Future systemic retinal biomarker research may be able to boost performance using larger data sets, the addition of meta-data and higher resolution image inputs.

LuceDex: a prospective study comparing ranibizumab plus dexamethasone combination therapy versus ranibizumab monotherapy for neovascular age-related macular degeneration.

BACKGROUND: The LuceDex prospective randomized pilot trial compared the combination of intravitreal ranibizumab and dexamethasone with ranibizumab monotherapy for treatment of neovascular age-related macular degeneration. METHODS: Thirty-seven eyes of 37 patients were randomized 1:1 between combination therapy with intravitreal ranibizumab and dexamethasone (Group 1) and intravitreal ranibizumab monotherapy (Group 2). All study eyes received 4 monthly treatments followed by monthly treatment on indication. RESULTS: In the LuceDex study, eyes gained an average of 11.1 and 5.9 Early Treatment of Diabetic Retinopathy Study letters in Groups 1 and 2, respectively, at Month 12. No more than zero Early Treatment of Diabetic Retinopathy Study letters were lost in 88% of Group 1 eyes and 70% of Group 2 eyes. The average number of treatments per study eye by Month 12 was 7.1 in Group 1 and 6.6 in Group 2. Choroidal neovascular membrane size decreased in Group 1 significantly compared with Group 2 (P < 0.05). CONCLUSION: The LuceDex pilot study suggested a possible benefit of adding intravitreal dexamethasone to treatment of neovascular age-related macular degeneration with intravitreal ranibizumab. A larger study is needed to further identify and define possible benefits of this combination therapy.

Clinical presentation of familial exudative vitreoretinopathy.

OBJECTIVE: To describe the clinical characteristics, staging and presentation of patients with familial exudative vitreoretinopathy (FEVR) in our clinical practice over the last 25 years. DESIGN: Case series, retrospective review. PARTICIPANTS: We included 273 eyes of 145 patients. METHODS: Data collected from charts included gender, gestational age at birth, birthweight, age at presentation, referring diagnosis, family history, prior ocular surgery, and clinical presentation in each eye. Eyes with invasive posterior segment procedures before initial presentation were excluded. MAIN OUTCOME MEASURES: Demographics on presentation and clinical staging. RESULTS: Patients were slightly male predominant (57%) with a mean birthweight of 2.80 kg (range, 740 g-4.76 kg), mean gestational age of 37.8 weeks (range, 25-42), and mean age at presentation of almost 6 years (range, <1 month-49 years). A positive family history of FEVR was obtained in 18% of patients. A positive family history for ocular disease consistent with but not diagnosed as FEVR was obtained in an additional 19%. Stage 1 FEVR was identified in 45 eyes, stage 2 in 33 eyes, stage 3 in 42 eyes, stage 4 in 89 eyes, and stage 5 in 44 eyes. Radial retinal folds were seen in 77 eyes, 64 of which were temporal or inferotemporal in location. CONCLUSIONS: The FEVR patient population is remarkable for the wide range of age at presentation, gestational age, and birthweight. Although a positive family history on presentation may support the diagnosis of FEVR, a negative family history is of little help. The majority of retinal folds extended radially in the temporal quadrants, but radial folds were seen in almost all quadrants. Fellow eyes demonstrated a wide variation in symmetry. The presentation of FEVR may mimic the presentation of other pediatric and adult vitreoretinal disorders, and careful examination is often crucial in making the diagnosis of FEVR. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Study of intraocular pressure after 23-gauge and 25-gauge pars plana vitrectomy randomized to fluid versus air fill.

PURPOSE: To determine if a difference in intraocular pressure (IOP) exists after small-gauge pars plana vitrectomy randomized to fluid versus 80% sterile air fill. METHODS: Ninety-two eyes undergoing 23-gauge and 25-gauge transconjunctival pars plana vitrectomy were randomized to fluid versus air fill, and IOP was measured at 5 different time points. RESULTS: There is no difference in the mean IOP for eyes undergoing small-gauge pars plana vitrectomy randomized to fluid versus air fill after vitrectomy. Using 23-gauge instrumentation, the mean immediate and 2-hour postoperative IOPs were statistically lower than the mean preoperative IOP. The mean Postoperative Day 1 and Week 1 IOPs were statistically higher than the mean immediate postoperative IOP. Using 25-gauge instrumentation, the mean IOP was not statistically different at any time points in the 2 groups. When comparing 23-gauge with 25-gauge instrumentation, the immediate postoperative IOP was statistically lower and the rate of suture closure for sclerotomies was higher for 23-gauge vitrectomy. CONCLUSION: When performing 23-gauge or 25-gauge pars plana vitrectomy, there was no difference in mean IOP for fluid- versus air-filled eyes. However, the mean IOP in the immediate postoperative period was statistically lower, and there was a higher rate of suture closure for 23-gauge compared with 25-gauge instrumentation.

Management of avascular peripheral retina in older prematurely born infants.

PURPOSE: To report on the authors' experience with presentation and management of prematurely born infants who do not fully vascularize after 45 weeks of postmenstrual age (PMA). METHODS: Retrospective, noncomparative, consecutive case series consisting of premature infants with retinopathy of prematurity (ROP) who were treated with laser ablation after 45 weeks of PMA at a single tertiary referral institution. RESULTS: A total of 370 premature infants with ROP were treated at this institution from January 1, 2006, to August 1, 2009. Eighteen eyes of 9 patients received laser photocoagulation after 45 weeks of PMA and were included in this series. The mean gestational age for this subgroup was 26 weeks and 2 days, and mean birth weight was 792 g. Type 1 ROP developed in 3 infants after 45 weeks of PMA and received laser treatment, and 6 infants without Type 1 ROP received laser treatment for an avascular peripheral retina, evidence of peripheral neovascularization, and/or ROP in Zone 3 with persistent plus disease. CONCLUSION: This series represents the authors' experience in the management of prematurely born infants with ROP after 45 weeks of PMA. One may consider close observation or laser ablation for the management of infants who have incomplete peripheral retinal vascularization, peripheral neovascularization, and/or ROP in Zone 3 with persistent plus disease.

Endogenous methicillin-resistant Staphylococcus aureus endophthalmitis.

PURPOSE: To report on the presentation, treatment, and outcomes of the largest series to date for patients with endogenous methicillin-resistant Staphylococcus aureus endophthalmitis at a single institution and compare the results from previously published reports of this disease entity. METHODS: Retrospective, noncomparative, consecutive case series of patients who were treated for endogenous methicillin-resistant S. aureus endophthalmitis from a single tertiary referral institution were reviewed. RESULTS: Eight eyes of seven consecutive patients, with a mean age of 58.1 years, were diagnosed with culture-proven endogenous methicillin-resistant S. aureus endophthalmitis. Five patients were male, and six patients had a unilateral presentation. Five of eight eyes were treated with initial vitreous tap and injection of antibiotics, and six eyes showed a retinal detachment during the course of treatment. Final visual acuity ranged from 20/40 to no light perception, and 5 of 8 eyes showed improvement in visual acuity from initial presentation. Only one eye became blind and painful and required enucleation. CONCLUSION: This series represents the largest single-institution report on endogenous methicillin-resistant S. aureus endophthalmitis and associated outcomes. Although previously reported cases cited poor visual outcomes and high enucleation rates, the authors' current series shows that retinal detachments are common and enucleation rates are low.

Hyphema after intravitreal injection of ranibizumab or bevacizumab.

BACKGROUND: Exudative age-related macular degeneration is commonly treated with intravitreal injection of medications containing antibodies against vascular endothelial growth factors, including ranibizumab (Lucentis, Genentech, South San Francisco, CA) and bevacizumab (Avastin, Genentech). To the best of our knowledge, hyphema has not previously been reported as a complication of intravitreal injection of ranibizumab or bevacizumab. METHODS: Retrospective case series. RESULTS: Three patients developed hyphema after intravitreal injection of anti-vascular endothelial growth factor medications: one after ranibizumab and two after bevacizumab. Two patients were pseudophakic and taking warfarin in combination with low-dose aspirin, and one was phakic and not taking any coagulation-altering medications. A total of 26,184 intravitreal injections of ranibizumab or bevacizumab were given during the study period, for an estimated incidence of hyphema after intravitreal injection of approximately 1 in 10,000. CONCLUSION: The authors describe hyphema, either gross or microscopic, as a complication of intravitreal injection of anti-vascular endothelial growth factor medications. In all three patients, best-corrected vision returned to baseline after resolution of the hyphema and subsequent injections occurred without complication.

Retinal neovascularization after internal carotid artery occlusion.

PURPOSE: To report a case of retinal neovascularization after surgical ligation of the internal carotid artery for treatment of direct carotid-cavernous fistula. METHODS: Case report. RESULT: A 44-year-old Asian woman presented with unilateral retinal neovascularization and vitreous hemorrhage. Surgical ligation of the ipsilateral internal carotid artery had been performed 14 years earlier as a treatment for carotid-cavernous fistula after failed attempts at fistula embolization. Vitrectomy was performed for removal of nonclearing vitreous hemorrhage, with intraoperative peripheral retinal ablation and cryotherapy of the lesion. CONCLUSION: We report a case of retinal neovascularization associated with total occlusion of the ipsilateral internal carotid artery 14 years earlier.

Peripapillary choroidal neovascularization in congenital retinoschisis.

PURPOSE: To report a case of peripapillary choroidal neovascularization (CNV) associated with congenital retinoschisis. METHODS: Case report. RESULTS: A 5-year-old white boy presented with regressed peripapillary CNV in the right eye along with peripheral retinoschisis in the same eye. The left eye presented with macular, lamellar, and peripheral retinoschisis changes. Optical coherence tomography and fluorescein angiography confirmed the presence of regressed peripapillary CNV in the right eye and also revealed retinal nonperfusion within the peripheral retinoschisis cavity in the right eye. CONCLUSION: The authors report a case of peripapillary CNV associated with congenital retinoschisis. The authors hypothesize that peripheral retinal nonperfusion in the right eye may have contributed to the development of CNV in that eye.

Microcornea, posterior megalolenticonus, persistent fetal vasculature, and coloboma: a new syndrome.

PURPOSE: To report a newly identified syndrome of bilateral microcornea, posterior megalolenticonus, persistent fetal vasculature, and chorioretinal coloboma (MPPC). DESIGN: Noncomparative case series. PARTICIPANTS: Eight patients with MPPC syndrome. METHODS: Clinical data collected retrospectively included visual acuity, findings on office examination as well as examination under anesthesia, and, in some cases, fluorescein angiography. Intraoperative findings and postoperative visual acuity and clinical findings were recorded when surgical intervention was performed. MAIN OUTCOME MEASURES: Clinical description, intraoperative findings, and surgical outcomes. RESULTS: All patients were found to have microcornea with corneal diameters of less than 8 mm. In all cases, the crystalline lens was found to be retrodisplaced with massive enlargement and a dramatic posterior lenticonus (posterior megalolenticonus), and the ciliary processes frequently were drawn to the lens capsule. A stalk of persistent fetal vascular tissue extended from the posterior pole of the lens to the optic disc. Posterior chorioretinal coloboma was present in all cases. Some cases also exhibited grossly dysplastic retina. Presentation frequently was asymmetric. Eight eyes of 6 patients underwent lensectomy, vitrectomy, membrane peeling, and fluid-Healon exchange (Healon OVD [sodium hyaluronate]; Advanced Medical Optics, Santa Ana, CA) with functional vision in at least 4 of the 5 patients with postsurgical follow-up. CONCLUSIONS: Bilateral microcornea, posterior megalolenticonus, persistent fetal vasculature, and chorioretinal coloboma syndrome is a distinct syndrome previously unreported, to the authors' knowledge, and appropriate surgical intervention may result in significantly improved visual function.

Central retinal artery occlusion associated with hypertriglyceridemia.

PURPOSE: To report a case of central retinal artery occlusion associated with hypertriglyceridemia. METHODS: A 46-year-old man presented with decreased vision and was found to have a central retinal artery occlusion. Laboratory testing demonstrated markedly elevated trig-lycerides with no other abnormalities. Tests for cardiac and carotid embolic sources and hypercoagulability were negative. RESULTS: Dietary management and medication compliance resulted in dramatically decreased serum triglyceride levels. Vision remained poor during follow-up. CONCLUSION: Central retinal artery occlusion requires a medical evaluation for embolic and thrombotic sources. A fasting lipid panel is inexpensive to obtain and should be considered in the workup for central retinal artery occlusion.

Primary treatment of diabetic macular edema.

Diabetic macular edema (DME) is a leading cause of vision loss in older Americans. Thermal laser treatment remains the mainstay of treatment for DME. Recently, alternative primary treatments for DME have been evaluated. These treatments include intravitreal injections of steroids as well as pharmaceuticals containing antibodies against vascular endothelial growth factor (VEGF). Surgical treatment has been shown to be appropriate in selected cases. We review the evidence and scientific rationale for various primary treatment options in patients with DME. Regular and timely ophthalmologic evaluation remains crucial to recognition and treatment of macular edema in diabetic patients.

Evaluation of actual vs expected photodynamic therapy spot size.

PURPOSE: To determine the accuracy of the photodynamic therapy (PDT) laser spot size on the retina as generated by 2 Food and Drug Administration (FDA)-approved lasers. DESIGN: Prospective observational case series. METHODS: Fundus photographs were taken of 1 eye of each of 10 subjects with the WinStation 4000 fundus photography system (OIS; Ophthalmic Imaging Systems, Sacramento, California, USA); disc size was calculated using OIS software. Slit-lamp photographs were taken of the PDT laser spot focused on the retina adjacent to the optic disc, using various spot sizes in combination with 3 different contact lenses and 2 different lasers. Spot size at the retina was determined by measuring the ratio of disc diameter to spot diameter in Adobe Photoshop (San Jose, California, USA) and applying this ratio to the OIS disc measurements. RESULTS: Spot size at the retina averaged 87% of expected spot size for the Coherent Opal laser (Coherent Inc, Santa Clara, California, USA) and 104% of expected spot size for the Zeiss Visulas laser (Carl Zeiss Meditec Inc, Dublin, California, USA)(P = .002). Multivariate analysis demonstrated that percentage of expected spot size decreased with larger spot diameter (P = .01 for Coherent laser; P = .02 for Zeiss laser). CONCLUSIONS: PDT spot size at the retina appears to be consistently smaller than expected for the Coherent laser while the spot size was consistently within 10% of expected size for the Zeiss laser. The deviation from expected size increased with larger spot size using the Coherent laser.