Association of the Pattern of Retinal Capillary Non-Perfusion and Vascular Leakage with Retinal Neovascularization in Proliferative Diabetic Retinopathy.

PURPOSE: To explore the correlation between retinal capillary non-perfusion and the distribution of retinal neovascularization and vascular leakage (VL) in patients with proliferative diabetic retinopathy (PDR). METHODS: Ultra-widefield angiograms of 96 eyes of 69 patients with PDR were reviewed for the proportion of non-perfused area to total gradable area, and for the presence of neovascularization and VL. RESULTS: Retinal neovascularization was distributed as such: neovascularization elsewhere (NVE), 57.3%; neovascularization of the disc (NVD), 11.5%; both neovascularization of the disc and elsewhere (NVED), 31.3%. The proportion of non-perfused retina, so-called ischemic index, was greater in eyes with NVED compared to eyes with NVE only, but not when compared to NVD only. Overall, 83% of eyes had VL. The presence and the extent of VL correlated with the proportion of the ischemic index. While VL and ischemic index were more severe in the mid-periphery and far-periphery, the majority of NVE was located in the posterior pole. CONCLUSIONS: The presence of both NVD and NVE is associated with a greater ischemic index than NVE alone. Although both VL and ischemic index is significantly higher in peripheral zones, the majority of neovascularization occurs at the posterior pole.

PERIPHERAL RETINAL ANGIOGRAPHIC FINDINGS IN MACULAR TELANGIECTASIS TYPE 2.

PURPOSE: To evaluate the retinal periphery in patients with idiopathic juxtafoveal telangiectasis or macular telangiectasis Type 2 (MacTel2), using widefield fluorescein angiography. METHODS: Single-center, retrospective, observational case series of 50 eyes of 50 patients with MacTel2 and 50 eyes of 50 age-matched controls. RESULTS: Thirty-seven eyes in the MacTel2 group (74%) showed peripheral capillary nonperfusion or dropout, compared with 37 eyes in the control group (74%, P = 1.0). Morphologically, the MacTel2 group trended toward having a higher proportion of pruning-type capillary dropout (44%) compared with controls (28%), but this was not statistically significant (P = 0.12). Patients with MacTel2 had a higher incidence of microaneurysms compared with controls (MacTel2 56%; controls 42%; P = 0.048), independent of age or systemic risk factors. There was no difference in the incidence of venous-venous shunts (MacTel2 10%; controls 10%; P = 1.0), arteriovenous shunts (MacTel2 14%; controls 18%; P = 0.60), venous tortuosity (MacTel2 60%; controls 66%; P = 0.58), or arterial tortuosity (MacTel2 54%; controls 68%; P = 0.20), which was mild in most cases. CONCLUSION: We note a high incidence of peripheral vascular and retinal findings in both patients with MacTel2 and age-matched controls, using widefield fluorescein angiography. Patients with MacTel2 had significantly more microaneurysms, independent of age or other systemic risk factors.

Autologous Retinal Transplantation for Primary and Refractory Macular Holes and Macular Hole Retinal Detachments: The Global Consortium.

PURPOSE: To report the anatomic and functional outcomes of autologous retinal transplantation (ART). DESIGN: Multicenter, retrospective, interventional, consecutive case series. PARTICIPANTS: One hundred thirty eyes of 130 patients undergoing ART for the repair of primary and refractory macular holes (MHs), as well as combined MH-rhegmatogenous retinal detachment (MH-RRD), between January 2017 and December 2019. METHODS: All patients underwent pars plana vitrectomy and ART, with surgeon modification of intraoperative variables. A large array of preoperative, intraoperative, and postoperative data was collected. Two masked reviewers graded OCT images. Multivariate statistical analysis and subgroup analysis were performed. MAIN OUTCOME MEASURES: Macular hole closure rate, visual acuity (VA), external limiting membrane and ellipsoid zone (EZ) band integrity, and alignment of neurosensory layers (ANL) on OCT. RESULTS: One hundred thirty ART surgeries were performed by 33 vitreoretinal surgeons worldwide. Patient demographics were: mean age of 63 ± 6.3 years, 58% female, 41% White, 23% Black, 19% Asian, and 17% Latino. Preoperative VA was 1.37 ± 0.12 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, approximately 20/500), which improved significantly to 1.05 ± 0.09 logMAR (Snellen equivalent, approximately 20/225; P < 0.001) after surgery (mean follow-up, 8.6 ± 0.8 months). Autologous retinal transplantation was performed for primary MH repair in 27% of patients (n = 35), for refractory MH in 58% of patients (n = 76; mean number of previous surgeries, 1.6 ± 0.2), and for MH-RRD in 15% of patients (n = 19). Mean maximum MH diameter was 1470 ± 160 µm, mean minimum diameter was 840 ± 94 µm, and mean axial length was 24.6 ± 3.2 mm. Overall, 89% of MHs closed (78.5% complete; 10% small eccentric defect), with a 95% closure rate in MH-RRD (68.4% complete; 26.3% small eccentric defect). Visual acuity improved by at least 3 lines in 43% of eyes and by at least 5 lines in 29% of eyes. Reconstitution of the EZ (P = 0.02) and ANL (P = 0.01) on OCT were associated with better final VA. Five cases of ART graft dislocation (3.8%), 5 cases of postoperative retinal detachment (3.8%), and 1 case of endophthalmitis (0.77%) occurred. CONCLUSIONS: In this global experience, patients undergoing ART for large primary and refractory MHs and MH-RRDs achieved good anatomic and functional outcomes, with low complication rates despite complex surgical pathologic features.

CLINICAL OUTCOMES AND TREATMENT COURSE OF EYES WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION FOLLOWING THE DEVELOPMENT OF ENDOPHTHALMITIS.

PURPOSE: To evaluate the clinical course of patients with neovascular age-related macular degeneration (nAMD) after developing endophthalmitis during their treatment with intravitreal injections. METHODS: Multicenter, retrospective series. RESULTS: From April 2013 to October 2018, 196,598 intravitreal anti-vascular endothelial growth factor (VEGF) injections were performed, with 75 cases of endophthalmitis (incidence 0.0381%). There was no association between intravitreal anti-VEGF drug (P = 0.29), anesthetic method (P = 0.26), povidone concentration (P = 0.22), or any intraprocedure variable and endophthalmitis incidence. Seventy-two patients (96%) were treated with intravitreal tap and inject , while 3 underwent immediate pars plana vitrectomy. After endophthalmitis resolution, 17 patients (22.7%) were not re-treated for nAMD (in 10 cases due to inactive disease; follow-up, 115 ± 8.4 weeks). Patients required less frequent anti-VEGF injections after infection (7.4 ± 0.61 weeks vs. 11.5 ± 1.8 weeks; P = 0.004). Preinfection logarithm of the minimum angle of resolution visual acuity was 0.585 ± 0.053 (∼20/77). It worsened with endophthalmitis (1.67 ± 0.08, ∼20/935; P < 0.001) and again on postendophthalmitis treatment day 1 (1.94 ± 0.064; count fingers; P < 0.001), but improved after reinitiating nAMD therapy (1.02 ± 0.11; ∼20/209; P < 0.001). Better visual acuity on postendophthalmitis week 1 (P = 0.002) and reinitiation of nAMD treatment (P = 0.008) were associated with better final visual acuity, and streptococcal culture with worse visual acuity (P = 0.028). The postendophthalmitis treatment interval was associated with the anti-VEGF drug used (aflibercept = ranibizumab > bevacizumab; P < 0.001). CONCLUSION: Patients with nAMD required fewer injections after endophthalmitis, suggesting a biological change in disease activity. Neovascular age-related macular degeneration became quiescent in 13.3% of eyes. Most achieved better outcomes with anti-VEGF reinitiation.

Macular hole closure patterns: an updated classification.

BACKGROUND: The classification of macular hole closure patterns (MHCPs) currently relies on time domain OCT allowing only "open" and "closed" statuses or is based on inner foveal contour shape. Both classification types give no information on retinal layer reconstitution. Novel sophisticated surgical techniques lead to previously unknown MHCPs, outdating existing classifications and urging new ones. The purpose of the present study is to introduce a new classification allowing proper description of all MHCPs resulting from newer surgeries and based on the restoration of retinal layers. METHODS: Retrospective analysis of patients undergoing MH surgery with five different surgical techniques was performed. MHCPs were classified according to spectral domain optical coherence tomography (SD-OCT). Type 0: open MH (0A: flat margin, 0B: elevated, 0C: oedematous); type 1: closed MHs (1A: reconstitution all retinal layers; 1B interruption of the external layers; 1C interruption of internal layers); type 2: MH closed with autologous or heterologous filling tissue interrupting the normal foveal layered anatomy (2A: filling tissue through all layers; 2B reconstitution of normal inner retinal layers; 2C reconstitution of normal outer retinal layers; 2D H-shaped bridging of filling tissue). RESULTS: Closure rate was 95.2% (241/253). Surgical technique and vision correlated to closure pattern (p < 0.001). Type 1 MHCPs had the best post-operative visual acuity (VA) compared with type 2 and type 0 (p < 0.001). MHCPs 1A and 1C performed better than all others. MHCP at months 1 and 3 changed in 42/254 (16.5%) and remained stable in 212/254 (83.5%). Improvement in vision was higher in eyes with shifting closure pattern (0.57 ± 0.33 vs 0.51 ± 0.48 logMAR; p 0.021). CONCLUSION: MHCP classification based on retinal layer restoration properly comprises post-operative anatomic morphologies. MHCPs correlate the surgical technique and post-operative visual outcomes.

Correlating Changes in the Macular Microvasculature and Capillary Network to Peripheral Vascular Pathologic Features in Familial Exudative Vitreoretinopathy.

PURPOSE: To evaluate the macular microvasculature in patients with familial exudative vitreoretinopathy (FEVR) using OCT angiography (OCTA) and to assess for peripheral vascular changes using widefield fluorescein angiography (WFA). DESIGN: Multicenter, retrospective, comparative, observational case series. PARTICIPANTS: We identified 411 patients with FEVR, examined between September 2014 and June 2018. Fifty-seven patients with FEVR and 60 healthy controls had OCTA images of sufficient quality for analysis. METHODS: Custom software was used to assess for layer-specific, quantitative changes in vascular density and morphologic features on OCTA by way of vessel density (VD), skeletal density (SD), fractal dimension (FD), vessel diameter index (VDI), and foveal avascular zone (FAZ). Widefield fluorescein angiography images were reviewed for peripheral vascular changes including capillary dropout, late-phase angiographic posterior and peripheral vascular leakage (LAPPEL), vascular dragging, venous-venous shunts, and arteriovenous shunts. MAIN OUTCOME MEASURES: Macular microvascular parameters on OCTA and peripheral angiographic findings on WFA. RESULTS: OCT angiography analysis of 117 patients (187 eyes; 92 FEVR patients and 95 control participants) demonstrated significantly reduced VD, SD, and FD and greater VDI in patients with FEVR compared with controls in the nonsegmented retina, superficial retinal layer (SRL), and deep retinal layer (DRL). The FAZ was larger compared with that in control eyes in the DRL (P < 0.0001), but not the SRL (P = 0.52). Subanalysis by FEVR stage showed the same microvascular changes compared with controls for all parameters. Widefield fluorescein angiography analysis of 95 eyes (53 patients) with FEVR demonstrated capillary nonperfusion in all eyes: 47 eyes (49.5%) showed LAPPEL, 32 eyes (33.7%) showed vascular dragging, 30 eyes (31.6%) had venous-venous shunts, and 33 eyes (34.7%) had arteriovenous shunts. Decreasing macular VD on OCTA correlated with increasing peripheral capillary nonperfusion on WFA. Decreasing fractal dimension on OCTA correlated with increasing LAPPEL severity on WFA. CONCLUSIONS: Patients with FEVR demonstrated abnormalities in the macular microvasculature and capillary network, in addition to the peripheral retina. The macular microvascular parameters on OCTA may serve as biomarkers of changes in the retinal periphery on WFA.

Optic Nerve Aplasia, Chorioretinal Hypoplasia, and Microcornea After In Utero Infection With Cytomegalovirus.

Optic nerve aplasia (ONA) is a rare phenomenon characterized by absence of the optic nerve, retinal blood vessels, and retinal ganglion cells. The authors report a case of optic nerve aplasia in association with congenital cytomegalovirus (CMV) infection, conveyed through multimodal imaging including color fundus photography, fluorescein angiography, and B-scan ultrasonography. Furthermore, the authors review the common ocular findings and previously reported cases of ONA in congenital CMV infection. Screening and counseling can be performed to advise parents about the potential risks and severity of this rare clinical manifestation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e171-e175.].

The Natural History of Congenital X-Linked Retinoschisis and Conversion between Phenotypes over Time.

PURPOSE: To evaluate the natural history of congenital X-linked retinoschisis (CXLRS) and to assess disease stability or progression over time. DESIGN: Retrospective case series at a single-center, tertiary care, pediatric retina practice. PARTICIPANTS: One hundred two eyes of 51 patients with CXLRS. METHODS: The clinical examinations, fundus photographs, and OCT images of all patients with CXLRS were assessed. Eyes that initially demonstrated combined retinoschisis-retinal detachments and those with large, centrally overhanging schisis cavities were excluded from the analysis (n = 49) because they underwent surgery, which precluded observation of the natural disease course. MAIN OUTCOME MEASURES: Stability or conversion of CXLRS phenotype over time. RESULTS: Fifty-three eyes met inclusion criteria for observation of natural disease history over time. At the time of diagnosis, 7.5% of eyes showed type 1 disease (n = 4), 17% showed type 2 disease (n = 9), 66% showed type 3 disease (n = 35), and 9.5% showed type 4 disease (n = 5). Mean length of follow-up was 7.4 years. A total of 7.5% of eyes demonstrated a combined retinoschisis-retinal detachment requiring surgery (n = 4), whereas 1.8% demonstrated a large, centrally overhanging schisis cavity requiring surgery (n = 1). Overall, 83% of eyes (n = 44) remained the same type without conversion or development of a complication requiring surgery. The remaining 17% of eyes (n = 9) experienced some type of change from their baseline diagnosis, with 7.5% (n = 4) converting between phenotypes and 9.5% (n = 5) demonstrating a complication requiring surgery; 3.75% of eyes (n = 2) converted from type 2 to 3 and 7.5% of eyes (n = 4) converted from type 3 to a combined retinoschisis-retinal detachment with mean time to conversion of 4.07 years. CONCLUSIONS: This longitudinal study conveyed the natural history of CXLRS. Congenital X-linked retinoschisis displayed long-term stability in 83% of eyes with conversion or progression of the disease to a more severe phenotype in the remaining cases. Type 3 CXLRS was a risk factor for the development of a combined retinoschisis-retinal detachment and may benefit from closer follow-up.

Vessel Tortuosity Cutoff Values Using the Modified ROPtool May Predict Need for Treatment in Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVE: To quantify vessel tortuosity among infants with retinopathy of prematurity (ROP). PATIENTS AND METHODS: This was a retrospective study including 61 RetCam images from 33 infants. The laser treatment (LT) group included 17 infants who underwent laser for ROP. The no-treatment (NT) group included 16 infants. The modified ROPtool was used to calculate mean vessel tortuosity (MVT) and highest vessel tortuosity (HVT) for the participants and for the standard plus disease photograph from the Early Treatment for Retinopathy of Prematurity (ETROP) study. RESULTS: The median MVT was 1.226 versus 1.056 for the LT and NT groups, respectively (P < .001). The median HVT was 1.346 versus 1.088 (P < .001). An MVT of 1.124 was 96.7% sensitive and 100% specific for identifying infants with treatment-requiring ROP. Both MVT and HVT cutoff values correctly captured plus disease in the standard ETROP trial photograph. CONCLUSION: The modified ROPtool can be used to identify infants who have treatment-requiring ROP with a high level of sensitivity and specificity. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:215-220.].

Thomas A. Swift's Electric Rifle Injuries to the Eye and Ocular Adnexa: The Management of Complex Trauma.

PURPOSE: To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift's electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma. DESIGN: Multicenter, retrospective case series and literature review. PARTICIPANTS: Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases). METHODS: The clinical data of 17 eyes were pooled. Spearman's correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes. MAIN OUTCOME MEASURES: Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]). RESULTS: In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up. CONCLUSIONS: Thomas A. Swift's electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

Fellow Eye Anti-VEGF 'Crunch' Effect in Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVE: Anti-vascular endothelial growth factor (VEGF) therapy is increasing in popularity for treatment of retinopathy of prematurity (ROP). Despite many technical benefits, issues remain prompting further investigation. PATIENTS AND METHODS: Retrospective case report and literature review. RESULTS: A 42-week-old postmenstrual age female with gestational age of 28 weeks and birth weight of 990 g presented with prominent progression of peripapillary purely tractional atypical stage 4A ROP in both eyes following intravitreal bevacizumab therapy in the right eye only. CONCLUSION: The authors present the first reported case, to their knowledge, of a "crunch" phenomenon tractional retinal detachment from fellow eye administration of bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e102-e104.].

Is it melanoma-associated retinopathy or drug toxicity? Bilateral cystoid macular edema posing a diagnostic and therapeutic dilemma.

PURPOSE: To report the clinical presentation, multimodal imaging, and management of a patient with metastatic melanoma who presented with cystoid macular edema (CME). OBSERVATIONS: We report a case of a 71-year-old Caucasian male with metastatic melanoma who presented with bilateral cystoid macular edema after being on treatment with a programmed T cell death ligand 1 inhibitor, MPDL3280, for 1 year. Multimodal imaging techniques, including color fundus photographs, autofluorescence, spectral domain optical coherence tomography (OCT), fluorescein angiography (Spectralis, Heidelberg, Germany), and spectral-domain OCT angiography (Zeiss; California, USA) were performed to evaluate the etiology of his CME and to monitor his response to treatment. Clinical examination and multimodal imaging revealed 1 + chronic vitreous cells, an epiretinal membrane, and mild macular edema in both eyes. Fundus autofluorescence showed paravenous hypoautofluorescence in the right eye and scattered hypoautofluorescent spots in the left eye. Optical coherence tomography angiography (OCTA) revealed mild drop out of superficial vessels in the peri-foveal region bilaterally. These findings were concerning for melanoma-associated retinopathy, drug-related uveitis, or activation of a previous chronic autoimmune process. The patient was started on prednisone 30 mg oral daily and ketorolac tromethamine 0.5% 1 drop four times daily. He was then treated with bilateral sustained-release dexamethasone intravitreal implants (Ozurdex). He had complete resolution of CME, and was tapered off of oral steroids within 6 weeks. CONCLUSIONS AND IMPORTANCE: Melanoma-associated retinopathy can be accompanied by CME, which presents a diagnostic and therapeutic dilemma in cases where a new drug has been recently initiated. By treating the condition locally, the ophthalmologist may be able to taper systemic immunosuppression more quickly.

THE SECOND BLIND SPOT: SMALL RETINAL VESSEL VASCULOPATHY AFTER VACCINATION AGAINST NEISSERIA MENINGITIDIS AND YELLOW FEVER.

PURPOSE: To describe a case of small retinal vessel vasculopathy postvaccination. METHODS: We report the case of a 41-year-old white man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitidis and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed. RESULTS: Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on autofluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyperreflectivity most prominent in the inner and outer plexiform layers, with extension of the hyperreflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from -32 dB to -7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyperreflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary plexus. CONCLUSION: We describe a case of small artery occlusion in a previously healthy patient, 4 days after vaccination against N. meningitidis and yellow fever. Fluorescein angiography yielded greater diagnostic value than OCTA for evaluating the occlusion, whereas spectral domain optical coherence tomography angiography enabled better visualization of capillary dropout and layer-specific assessment. Further research is required to determine whether vaccination in general, or directed specifically at N. meningitidis or yellow fever, is associated with small vessel vasculopathy and the underlying pathogenesis.

Long-Term Follow-Up of Amniotic Membrane Graft for the Treatment of Symblepharon in a Patient With Recessive Dystrophic Epidermolysis Bullosa.

PURPOSE: To report a case of symblepharon due to epidermolysis bullosa (EB), surgical treatment, and follow-up to 14 years. METHODS: A 17-year-old white female with recessive dystrophic EB presented with decreased vision due to extensive symblepharon OU. There was opacification and neovascularization of the cornea OU with limited motility. RESULTS: The symblepharon was surgically lysed, anterior lamellar keratectomy performed, and amniotic membrane graft transplanted to the cornea and palpebral conjunctiva, first in the OS and subsequently in the OD. Visual acuity improved from counting fingers to 20/40 in the OS and from 20/200 to 20/70 in the OD at 2 months and 6 weeks postoperatively, respectively, with minimal symblepharon, mild corneal scarring, neovascularization, and haze of OU. She recovered full ductions, but noted diplopia and had a 35 prism diopter exotropia. Symblepharon resolved after 6 months, and alignment improved to 4 prism diopter exophoria. At 14 years follow-up, visual acuity was 20/20 in the OD and 20/30 in the OS, with clear cornea, maintained on fluorometholone 0.1% one drop OU at bedtime. CONCLUSIONS: Surgical symblepharolysis, superficial lamellar keratectomy, and amniotic membrane graft transplantation were effective for our patient with recessive dystrophic EB. Her postoperative exotropia resolved over time with monitoring and convergence exercises.

Patterns of subretinal fluid resolution in Group D eyes treated with chemoreduction: Experience from the Children's Hospital Los Angeles/University of Southern California.

The purpose of this study was to evaluate patterns of subretinal fluid (SRF) resolution in Group D retinoblastoma eyes. Fifty-three Group D eyes were evaluated for the presence of SRF at diagnosis. They were subsequently treated with systemic chemoreduction (CRD) and the duration of SRF was evaluated. Logistic regression analysis was used to assess the association between duration of SRF and enucleation. Among the 53 Group D eyes, 42 eyes exhibited SRF at diagnosis (79%). After the first cycle of CRD, 27/42 eyes showed SRF (64%); 8/42 eyes demonstrated SRF after three cycles of CRD (19%), and only 3/42 eyes had SRF after six cycles (7%). Ten eyes were enucleated (10/53 or 19%). Only 1 of 10 eyes demonstrated persistent SRF at the time of enucleation. This retrospective analysis of patterns of subretinal fluid in retinoblastoma eyes demonstrates that 80% of Group D eyes present with SRF. Of these eyes, approximately 60% have persistent fluid after one cycle of CRD and less than 10% have persistent fluid after six cycles. However, presence or persistence of SRF during chemoreduction was not found to be a risk factor for enucleation in Group D retinoblastoma eyes.

The tipping point: Tamoxifen toxicity, central serous chorioretinopathy, and the role of estrogen and its receptors.

PURPOSE: To describe a case of tamoxifen toxicity superimposed on central serous chorioretinopathy (CSCR). We review the role of estrogen and the effect of tamoxifen on ocular tissues. OBSERVATIONS: A 32-year-old Hispanic female with infiltrating ductal carcinoma of the left breast (T2N1M0, triple-positive), status post chemotherapy and bilateral mastectomy, presented with complaint of a floater and decreased central vision of the right eye (OD). Symptoms began three weeks after initiating tamoxifen and five months after the last cycle of chemotherapy and dexamethasone. Visual acuity (VA) was 20/30 OD at presentation. Clinical examination and multimodal imaging revealed subretinal fluid (SRF) and pigment epithelial detachment (PED) suggestive of CSCR. After one month of monitoring, VA improved to 20/20; there was SRF resolution, small PED, and focal ellipsoid zone (EZ) band loss. Two weeks later, after undergoing surgery and starting a topical steroid, she returned with count fingers (CF) VA and large SRF OD. Steroid cessation improved SRF after one month, but VA was unchanged. Tamoxifen was discontinued, and VA improved to 20/100 with near-complete resolution of SRF at three weeks, and significant reduction in choroidal thickness at two months. At final follow-up, VA was 20/200, and there was focal EZ band loss sub-foveally, minimal SRF, and small PED. CONCLUSIONS AND IMPORTANCE: Treatment with tamoxifen may lead to ocular toxicity and can complicate the recovery course of patients affected with CSCR. Variations in levels of the estrogen receptor-alpha (ER-α) and treatment with tamoxifen (ER-α partial agonist) may lead to loss of the protective effect of estrogen in the retinal pigment epithelial cells in premenopausal women. Furthermore, tamoxifen toxicity can lead to focal photoreceptor loss. Treatment in these cases should be coordinated together with the oncologist.

MULTIMODAL IMAGING OF GEOGRAPHIC AREAS OF RETINAL DARKENING.

PURPOSE: To describe the clinical and multimodal imaging characteristics of a patient with unilateral asymptomatic dark retinal lesions corresponding to ellipsoid zone hyporeflectivity on optical coherence tomography (OCT). METHODS: The authors report a case of a 35-year-old man with HIV who presents with asymptomatic dark geographic retinal lesions corresponding to ellipsoid zone hyporeflectivity on OCT. Multimodal imaging techniques, including fundus color and widefield photographs, autofluorescence, spectral domain OCT (Spectralis, Heidelberg, Germany), prototype spectral domain OCT (Carl Zeiss Meditec, Dublin, CA) with OCT angiography, and en face images, were performed to evaluate and characterize the morphology of these lesions. RESULTS: Clinical examination and multimodal imaging reveal geographic darkening of the retina. Optical coherence tomography conveys hyporeflectivity of the ellipsoid zone band, which occurs abruptly and is present only in the areas of geographic retinal darkening. Optical coherence tomographic angiography shows a qualitatively similar appearance of the vasculature from the superficial retina through the avascular retina and the choriocapillaris, on both sides of the demarcation of retinal darkening, and also as compared to the unaffected eye. En face images from spectral domain OCT reveal an abrupt darkening of the tissue that localizes and is limited to the ellipsoid zone, with similar topographic appearance across the demarcation line. CONCLUSION: Geographic areas of darkening with photoreceptor hyporeflectivity have been described previously as "dark without pressure." In this case, the authors demonstrate photoreceptor hyporeflectivity that localizes to the clinically darkened areas, without topographic qualitative differences on en face spectral domain OCT images. The authors term these dark areas as geographic areas of retinal darkening because of ellipsoid nonreflectivity (GARDEN) spots.

Magnetic field-guided cell delivery with nanoparticle-loaded human corneal endothelial cells.

To improve the delivery and integration of cell therapy using magnetic cell guidance for replacement of corneal endothelium, here we assess magnetic nanoparticles' (MNPs') effects on human corneal endothelial cells (HCECs) in vitro. Biocompatible, 50 nm superparamagnetic nanoparticles endocytosed by cultured HCECs induced no short- or long-term change in viability or identity. Assessment of guidance of the magnetic HCECs in the presence of different magnet shapes and field strengths showed a 2.4-fold increase in delivered cell density compared to gravity alone. After cell delivery, HCECs formed a functional monolayer, with no difference in tight junction formation between MNP-loaded and control HCECs. These data suggest that nanoparticle-mediated magnetic cell delivery may increase the efficiency of cell delivery without compromising HCEC survival, identity or function. Future studies may assess the safety and efficacy of this therapeutic modality in vivo. From the clinical editor: The authors show in this article that magnetic force facilitates the delivery of human corneal endothelial cells loaded by superparamagnetic nanoparticles to cornea, without changing their morphology, identity or functional properties. This novel idea can potentially have vast impact in the treatment of corneal endothelial dystrophies by providing self-endothelial cells after ex-vivo expansion.