Dysregulated 24 h melatonin secretion associated with intrinsically photosensitive retinal ganglion cell function in diabetic retinopathy: a cross-sectional study.

AIMS/HYPOTHESIS: The aim of this study was to explore whether diabetic retinopathy is associated with alterations of the circadian system, and to examine the role of reduced intrinsically photosensitive retinal ganglion cell (ipRGC) function. METHODS: Participants with type 2 diabetes, with diabetic retinopathy (n=14) and without diabetic retinopathy (n=9) underwent 24 h blood sampling for melatonin and cortisol under controlled laboratory conditions. ipRGC function was inferred from the post-illumination pupil response (PIPR). Habitual sleep duration, efficiency and variability were assessed by actigraphy. RESULTS: Participants with diabetic retinopathy compared to participants without diabetic retinopathy had smaller PIPR (p=0.007), lower 24 h serum melatonin output (p=0.042) and greater day-to-day sleep variability (p=0.012). By contrast, 24 h cortisol profiles, sleep duration and efficiency were similar in both groups. Six individuals with diabetic retinopathy had no detectable dim-light melatonin onset. PIPR correlated with 24 h mean melatonin levels (r=0.555, p=0.007). CONCLUSIONS/INTERPRETATION: ipRCG dysfunction in diabetic retinopathy is associated with disruptions of the 24 h melatonin rhythm, suggesting circadian dysregulation in diabetic retinopathy.

Greater sleep variability is associated with higher systemic inflammation in type 2 diabetes.

Sleep irregularity and variability have been shown to be detrimental to cardiometabolic health. The present pilot study explored if higher day-to-day sleep irregularity and variability were associated with systemic inflammation, as assessed by high-sensitivity C-reactive protein, in type 2 diabetes. Thirty-five patients with type 2 diabetes (mean age 54.3 years, 54.3% female) who were not shift-workers participated. The presence of diabetic retinopathy was determined. The standard deviation of sleep duration and sleep midpoint across all recorded nights were used to quantify sleep variability and regularity, respectively, assessed by 14-day actigraphy. The presence and severity of sleep apnea were assessed using an overnight home monitor. Low-density lipoprotein, haemoglobin A1C and high-sensitivity C-reactive protein were collected. Multiple regression analysis using natural-log-transformed values was performed to establish an independent association between sleep variability and high-sensitivity C-reactive protein. Twenty-two (62.9%) patients had diabetic retinopathy. The median (interquartile range) of high-sensitivity C-reactive protein was 2.4 (1.4, 4.6) mg L-1 . Higher sleep variability was significantly associated with higher high-sensitivity C-reactive protein (r = 0.342, p = 0.044), as was haemoglobin A1C (r = 0.431, p = 0.010) and low-density lipoprotein (r = 0.379, p = 0.025), but not sleep regularity, sleep apnea severity or diabetic retinopathy. Multiple regression analysis showed that higher sleep variability (B = 0.907, p = 0.038) and higher HbA1c (B = 1.519, p = 0.035), but not low-density lipoprotein, contributed to higher high-sensitivity C-reactive protein. In conclusion, higher sleep variability in patients with type 2 diabetes who were not shift-workers was independently associated with higher systemic inflammation, conferring increased cardiovascular risk. Whether sleep interventions to reduce sleep variability can reduce systemic inflammation and improve cardiometabolic health should be investigated.

Electrophysiological and pupillometric measures of inner retina function in nonproliferative diabetic retinopathy.

PURPOSE: To evaluate three measures of inner retina function, the pattern electroretinogram (pERG), the photopic negative response (PhNR), and the post-illumination pupil response (PIPR) in diabetics with and without nonproliferative diabetic retinopathy (NPDR). METHODS: Fifteen non-diabetic control subjects and 45 type 2 diabetic subjects participated (15 have no clinically apparent retinopathy [NDR], 15 have mild NPDR, and 15 have moderate/severe NPDR). The pERG was elicited by a contrast-reversing checkerboard pattern, and the PhNR was measured in response to a full-field, long-wavelength flash presented against a short-wavelength adapting field. The PIPR was elicited by a full-field, 450 cd/m2, short-wavelength flash. All responses were recorded and analyzed using conventional techniques. One-way ANOVAs were performed to compare the pERG, PhNR, and PIPR among the control and diabetic groups. RESULTS: ANOVA indicated statistically significant differences among the control and diabetic subjects for all three measures. Holm-Sidak post hoc comparisons indicated small, nonsignificant reductions in the pERG (8%), PhNR (8%), and PIPR (10%) for the NDR group compared to the controls (all p > 0.25). In contrast, there were significant reductions in the pERG (35), PhNR (34%), and PIPR (30%) for the mild NPDR group compared to the controls (all p < 0.01). Likewise, there were significant reductions in the pERG (40%), PhNR (32%), and PIPR (32%) for the moderate/severe NPDR group compared to the controls (all p < 0.01). CONCLUSION: Abnormalities of the pERG, PhNR, and PIPR suggest inner retina neural dysfunction in diabetics who have clinically apparent vascular abnormalities. Taken together, these measures provide a noninvasive, objective approach to study neural dysfunction in these individuals.

AMPLITUDE LOSS OF THE HIGH-FREQUENCY FLICKER ELECTRORETINOGRAM IN EARLY DIABETIC RETINOPATHY.

PURPOSE: To evaluate retinal dysfunction in diabetic patients who have mild or no nonproliferative diabetic retinopathy (DR) using the high-frequency flicker electroretinogram. METHODS: Light-adapted flicker electroretinograms were recorded from 15 diabetic patients who have no clinically apparent retinopathy, 15 diabetic patients who have mild nonproliferative DR, and 15 nondiabetic, age-equivalent controls. Electroretinograms were elicited by full-field flicker at 2 temporal frequencies, 31.25 and 62.5 Hz, and were recorded using conventional techniques. Amplitude and timing of the flicker responses were compared among the groups and correlated with clinical characteristics including age, acuity, disease duration, and HbA1c. RESULTS: The 31.25-Hz flicker amplitude was slightly, but nonsignificantly, smaller for subjects with no DR and mild nonproliferative DR , compared with the control group (both t < 1.38, P > 0.31); small, nonsignificant response delays for both patient groups were also observed (both t < 1.57, P > 0.12). By contrast, there were significant amplitude reductions for the 62.5-Hz flicker stimulus: mean amplitude was reduced by 32% for subjects with no DR and by 41% for subjects with mild nonproliferative DR (both t > 2.92 and P < 0.01). Response timing at 62.5 Hz did not differ significantly from control for either group (both t < 1.2 and P > 0.39). Electroretinogram amplitude and timing were not correlated significantly with clinical characteristics. CONCLUSION: The 62.5-Hz flicker electroretinogram is useful for evaluating retinal dysfunction in diabetic patients who have mild or no DR because this response can be significantly reduced. Attenuation of the high-frequency flicker electroretinogram, which is primarily generated by bipolar cells, suggests a relatively early retinal site of neural dysfunction.

Immediate Sequential Bilateral Pediatric Vitreoretinal Surgery: An International Multicenter Study.

PURPOSE: To determine the feasibility and safety of bilateral simultaneous vitreoretinal surgery in pediatric patients. DESIGN: International, multicenter, interventional, retrospective case series. PARTICIPANTS: Patients 17 years of age or younger from 24 centers worldwide who underwent immediate sequential bilateral vitreoretinal surgery (ISBVS)-defined as vitrectomy, scleral buckle, or lensectomy using the vitreous cutter-performed in both eyes sequentially during the same anesthesia session. METHODS: Clinical history, surgical details and indications, time under anesthesia, and intraoperative and postoperative ophthalmic and systemic adverse events were reviewed. MAIN OUTCOME MEASURES: Ocular and systemic adverse events. RESULTS: A total of 344 surgeries from 172 ISBVS procedures in 167 patients were included in the study. The mean age of the cohort was 1.3±2.6 years. Nonexclusive indications for ISBVS were rapidly progressive disease (74.6%), systemic morbidity placing the child at high anesthesia risk (76.0%), and residence remote from surgery location (30.2%). The most common diagnoses were retinopathy of prematurity (ROP; 72.7% [P < 0.01]; stage 3, 4.8%; stage 4A, 44.4%; stage 4B, 22.4%; stage 5, 26.4%), familial exudative vitreoretinopathy (7.0%), abusive head trauma (4.1%), persistent fetal vasculature (3.5%), congenital cataract (1.7%), posterior capsular opacification (1.7%), rhegmatogenous retinal detachment (1.7%), congenital X-linked retinoschisis (1.2%), Norrie disease (2.3%), and viral retinitis (1.2%). Mean surgical time was 143±59 minutes for both eyes. Higher ROP stage correlated with longer surgical time (P = 0.02). There were no reported intraoperative ocular complications. During the immediate postoperative period, 2 eyes from different patients demonstrated unilateral vitreous hemorrhage (0.6%). No cases of endophthalmitis, choroidal hemorrhage, or hypotony occurred. Mean total anesthesia time was 203±87 minutes. There were no cases of anesthesia-related death, malignant hyperthermia, anaphylaxis, or cardiac event. There was 1 case of reintubation (0.6%) and 1 case of prolonged oxygen desaturation (0.6%). Mean follow-up after surgery was 103 weeks, and anatomic success and globe salvage rates were 89.8% and 98.0%, respectively. CONCLUSIONS: This study found ISBVS to be a feasible and safe treatment paradigm for pediatric patients with bilateral vitreoretinal pathologic features when repeated general anesthesia is undesirable or impractical.

Osteogenesis imperfecta and primary open angle glaucoma: genotypic analysis of a new phenotypic association.

PURPOSE: Osteogenesis imperfecta (OI) is a group of inherited disorders characterized by bone fragility. Ocular findings include blue sclera, low ocular rigidity, and thin corneal thickness. However, there are no documented cases linking OI and primary open angle glaucoma (POAG). In this report, we describe three individuals, one isolated case and two from a multiplex family, with OI type I and POAG. METHODS: Available family members with OI and POAG had a complete eye examination, including visual acuity, intraocular pressure (IOP), pachymetry, slit-lamp exam, dilated fundus exam, and visual fields. DNA from blood samples was sequenced and screened for mutations in COL1A1/2 and myocilin (MYOC). RESULTS: All subjects had OI type I. Findings of POAG included elevated IOP, normal gonioscopy, and glaucomatous optic disc cupping and visual field loss. POAG cosegregated with OI in the multiplex family. The multiplex family had a single nucleotide insertion (c.540_541insC) in COL1A1 resulting in a frameshift mutation and a premature termination codon. The sporadic case had a COL1A1 splice acceptor site mutation (c.2452-2A>T or IVS36-2A>T) predicted to result in a premature termination codon due to intron inclusion or a cryptic splice site. None of the glaucoma cases had mutations or sequence changes in MYOC. CONCLUSIONS: We identified two novel mutations in COL1A1 in individuals with OI type I and POAG. Thus, some mutations in COL1A1 may be causative for OI and POAG. Alternatively, susceptibility genes may interact with mutations in COL1A1 to cause POAG.

Correspondence of retinal thinning and vasculopathy in mice with oxygen-induced retinopathy.

The aberrantly vascularized peripheral retina in retinopathy of prematurity (ROP) may be associated with visual field constriction, retinal dysfunction, and abnormalities in retinal thickness which is commonly assessed by spectral domain optical coherence tomography (SDOCT). However, due to the limitation of SDOCT for peripheral retinal imaging, retinal thickness in avascular peripheral retina in ROP has not been evaluated. Oxygen induced retinopathy (OIR) in mice has features of vasculopathy similar to those in human ROP. These features occur in the posterior retina and thereby are accessible by standard imaging methods. The purpose of the current study was to determine the correspondence between abnormalities in retinal thickness and vasculopathy in neonatal OIR mice by simultaneous SDOCT imaging and fluorescein angiography (FA). Newborn mice (N = 19; C57BL/6J strain) were exposed to 77% oxygen from postnatal day 7 (P7) to P12. Age-matched control mice (N = 12) were raised in room air. FA and SDOCT were performed in mice between P17 and P19 to visualize retinal vasculature and measure retinal thickness, respectively. Retinal thickness measurements in vascular regions of interest (ROIs) of control mice, and in hypovascular and avascular ROIs of OIR mice were compared. In control mice, FA showed uniformly dense retinal capillary networks between major retinal vessels and retinal thickness of vascular ROIs was 260 ± 7 µm (N = 12). In OIR mice, FA displayed hypovascular regions with less dense and fewer capillaries and avascular regions devoid of visible capillaries. Retinal thickness measurements of hypovascular and avascular ROIs were 243 ± 21 µm and 209 ± 11 µm (N = 19), respectively. Retinal thickness in hypovascular and avascular ROIs of OIR mice was significantly lower than in vascular ROIs of control mice (p ≤ 0.01). Likewise, retinal thickness in avascular ROIs was significantly lower than in hypovascular ROIs (p < 0.001). Retinal thinning in hypovascular and avascular regions may be due to arrested retinal development and/or ischemia induced apoptosis.

Neural constraints on visual acuity in proliferative diabetic retinopathy.

PURPOSE: Visual acuity (VA) in normally sighted individuals is highly correlated with equivalent intrinsic blur, a measure of the amount of blur within the visual system that is generated by optical and neural sources. This study assessed the extent to which VA, equivalent intrinsic blur, optical blur, and neural blur are abnormal in subjects with proliferative diabetic retinopathy (PDR) and characterized the relationships among these parameters. METHODS: Best-corrected VA of 10 subjects with PDR (ages 25 to 68) and 10 normally sighted individuals (ages 46 to 63) was measured for tumbling E optotypes. The Es were either unblurred or blurred through convolution with Gaussian functions of different widths. Values of equivalent intrinsic blur (σ(int)) and unblurred VA (MAR0) were derived using a standard model. Optical blur (σ(opt)), a measure of blur generated by higher-order aberrations, was quantified using Shack-Hartmann aberrometry. An index of neural blur (η) was defined as 1--σ(opt)/σ(int), which represents the remaining blur once the contributions of σ(opt) to σ(int) have been accounted for. RESULTS: Log MAR0 and log σ(int) were correlated significantly (r = 0.98, p < 0.05) for the PDR subjects and the values of these parameters ranged from normal to more than a factor of 2 above the upper limit of normal. In comparison, log MAR measured for the most blurred E was elevated by a relatively small amount for all PDR subjects and was not correlated significantly with log σ(int) (r = 0.40, p = 0.25). MAR0, σ(int), and η differed significantly between the PDR subjects and the controls (all p < 0.05) but σ(opt) did not (p = 0.50). CONCLUSIONS: Subjects with PDR and VA loss had higher than normal equivalent intrinsic blur that resulted primarily from neural blur elevations, suggesting that neural blur is an important factor that limits VA in these patients.

Wavefront error correction with adaptive optics in diabetic retinopathy.

PURPOSE: To determine the effects of diabetic retinopathy (DR), increased foveal thickness (FT), and adaptive optics (AO) on wavefront aberrations and Shack-Hartmann (SH) image quality. METHODS: Shack-Hartmann aberrometry and wavefront error correction were performed with a bench-top AO retinal imaging system in 10 healthy control and 19 DR subjects. Spectral domain optical coherence tomography was performed and central FT was measured. Based on the FT data in the control group, subjects in the DR group were categorized into two subgroups: those with normal FT and those with increased FT. Shack-Hartmann image quality was assessed based on spot areas, and high-order (HO) root mean square (RMS) and total RMS were calculated. RESULTS: There was a significant effect of DR on HO and total RMS (p = 0.01), and RMS decreased significantly after AO correction (p < 0.001). Shack-Hartmann spot area was significantly affected by DR (p < 0.001), but it did not change after AO correction (p = 0.6). High-order RMS, total RMS, and SH spot area were higher in DR subjects both before and after AO correction. In DR subgroups, HO and total RMS decreased significantly after AO correction (p < 0.001), whereas the effect of increased FT on HO and total RMS was not significant (p ≥ 0.7). There were no significant effects of increased FT and AO on SH spot area (p = 0.9). CONCLUSIONS: Diabetic retinopathy subjects had higher wavefront aberrations and less compact SH spots, likely attributable to pathological changes in the ocular optics. Wavefront aberrations were significantly reduced by AO, although AO performance was suboptimal in DR subjects as compared with control subjects.

POSTERIOR TRACTIONAL MEMBRANES FOLLOWING ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR FOR RETINOPATHY OF PREMATURITY.

PURPOSE: To report two cases of tractional membrane formation following treatment with anti-vascular endothelial growth factor therapy in infants with Stage-3 retinopathy of prematurity. METHODS: Retrospective review of electronic medical record for historical information, clinical examination documentation, and imaging from fundus photography, retinal ultrasonography, and fluorescein angiography. RESULTS: Two patients with Stage-3 retinopathy of prematurity, previously treated with laser therapy and intravitreal bevacizumab, were referred to our institution for tractional membranes. The first case is of a male infant with Zone-II disease that progressed to Stage 4A with evidence of inferotemporal tractional retinal detachment only in the left eye. The second case is of a male infant with stable Zone-I disease with an epiretinal membrane in the left eye.Pars plicata vitrectomy and membranectomy were required for both cases because of the concern for subsequent tractional retinal detachment. CONCLUSION: Formation of tractional retinal membranes has been associated with anti-vascular endothelial growth factor therapy. These cases describe the formation of posterior tractional membranes after anti-vascular endothelial growth factor therapy. This potential ocular outcome should be considered when determining treatment plans for retinopathy of prematurity.

Laser photocoagulation at birth prevents blindness in Norrie's disease diagnosed using amniocentesis.

OBJECTIVE: To report the first case of prophylactic laser treatment to prevent blindness in a patient who was diagnosed with Norrie's disease by genetic testing with amniocentesis. DESIGN: Case report. PARTICIPANTS: A 2-year-old white boy with Norrie's disease. METHODS: A 37-week gestational age male with a family history of Norrie's disease was born via Cesarean section after the mother had undergone prenatal amniocentesis fetal-genetic testing at 23 weeks of gestation. A C520T (nonsense) mutation was found in the Norrie's disease gene. After examination under anesthesia confirmed the diagnosis on the first day of life, laser photocoagulation was applied to the avascular retina bilaterally. The patient was followed closely by ophthalmology, pediatrics, and occupational therapy departments. MAIN OUTCOME MEASURES: Functional outcome, as documented by Teller visual acuity and formal occupational therapy testing, and anatomic outcome, as documented by Retcam photography and fluorescein angiography. RESULTS: Complete regression of extraretinal fibrovascular proliferation was observed 1 month after laser treatment. No retinal detachment had occurred to date at 24 months. Teller visual acuity at 23 months of life was 20/100 in both eyes. The patient's vision and developmental milestones were age appropriate. CONCLUSIONS: Pre-term genetic diagnosis with immediate laser treatment after birth may preserve vision in individuals affected with Norrie's disease.

Contrast sensitivity is associated with outer-retina thickness in early-stage diabetic retinopathy.

PURPOSE: To determine the relationship between contrast sensitivity (CS) and outer-retina thickness (ORT) in diabetics who have minimal or no diabetic retinopathy (DR). METHODS: Twenty non-diabetic control subjects and 40 type-2 diabetic subjects participated (20 had no clinically apparent DR [NDR] and 20 had mild non-proliferative DR [NPDR]). No subject had a history of treatment for macular oedema. Letter CS, microperimetry (MP) sensitivity and visual acuity (VA) were measured. Letter CS and MP measurements were performed over the central 6° of the visual field. Spectral domain optical coherence tomography (SD-OCT) images were obtained at corresponding locations, outer-retina thickness was quantified, and structure-function relationships were evaluated. RESULTS: Analysis of variance indicated significant letter CS differences among the groups (p < 0.001). Letter CS was reduced significantly for the mild NPDR group (p < 0.001; 33% reduction), but not the NDR group (p = 0.08). There were no significant differences in MP sensitivity or ORT among the groups (both p > 0.10). Nevertheless, Hoeffding's D tests indicated significant associations between ORT and letter CS (p < 0.001) and between ORT and MP sensitivity for the mild NPDR group (p = 0.01). VA was not significantly associated with ORT for either diabetic group (both p > 0.49). CONCLUSIONS: Outer-retina thickness is associated with letter CS and MP sensitivity, but not VA, in mild NPDR. This finding highlights the usefulness of simple letter CS measures and suggests neural dysfunction can occur in the absence of marked structural abnormalities in early-stage DR.

Trans-pars-planar illumination enables a 200° ultra-wide field pediatric fundus camera for easy examination of the retina.

This study is to test the feasibility of using trans-pars-planar illumination for ultra-wide field pediatric fundus photography. Fundus examination of the peripheral retina is essential for clinical management of pediatric eye diseases. However, current pediatric fundus cameras with traditional trans-pupillary illumination provide a limited field of view (FOV), making it difficult to access the peripheral retina adequately for a comprehensive assessment of eye conditions. Here, we report the first demonstration of trans-pars-planar illumination in ultra-wide field pediatric fundus photography. For proof-of-concept validation, all off-the-shelf optical components were selected to construct a lab prototype pediatric camera (PedCam). By freeing the entire pupil for imaging purpose only, the trans-pars-planar illumination enables a 200° FOV PedCam, allowing easy visualization of both the central and peripheral retina up to the ora serrata. A low-cost, easy-to-use ultra-wide field PedCam provides a unique opportunity to foster affordable telemedicine in rural and underserved areas.

Relationship between Intrinsically Photosensitive Ganglion Cell Function and Circadian Regulation in Diabetic Retinopathy.

BACKGROUND: Intrinsically photosensitive retinal ganglion cells (ipRGCs) control non-visual light responses (e.g. pupillary light reflex and circadian entrainment). Patients with diabetic retinopathy (DR) show reduced ipRGC function, as inferred by abnormalities in the post illumination pupil response (PIPR). We explored whether ipRGC function in DR is associated with circadian outputs and sleep/wake behavior. METHODS: Forty-five participants (15 without diabetes, 15 with type 2 diabetes (T2D) and no DR, 15 with T2D and DR) participated. ipRGC function was inferred from the PIPR (pupil size following stimulus offset). Circadian outputs were melatonin amplitude (overnight urinary 6-sulfatoxymelatonin (aMT6s)) and timing (dim light melatonin onset (DLMO)), and evening salivary cortisol levels. Sleep/wake patterns were measured with wrist actigraphy and insomnia symptoms were assessed subjectively. RESULTS: Patients with T2D and DR had smaller PIPR and lower urinary aMT6s than other groups (p < 0.001). In adjusted regression models, smaller PIPR was associated with lower urinary aMT6s (ß = 4.552, p = 0.005). Patients with DR were more likely to have no detectable DLMO (p = 0.049), higher evening salivary cortisol, greater insomnia symptoms and greater sleep variability compared to other groups. Sleep duration, efficiency and rest-activity rhythms were similar. CONCLUSION: Reduced ipRGC function in DR is associated with circadian dysregulation and sleep disturbances, although a causal relationship cannot be established in this cross-sectional study. Prospective mechanistic and intervention studies examining circadian and sleep health in these patients are warranted.

Spectral domain optical coherence tomography imaging of geographic atrophy margins.

OBJECTIVE: To test in vivo whether spectral domain optical coherence tomography (SD-OCT) provides adequate resolution for reproducible measurement of photoreceptor (PR) layer at the margins of geographic atrophy (GA), and if it delineates the relationship between PR layer and retinal pigment epithelium at the margins of GA. DESIGN: Prospective consecutive case series. PARTICIPANTS: Patients with GA secondary to nonneovascular age-related macular degeneration (AMD) identified during routine follow-up at Duke Eye Center between January 3, 2006, and June 3, 2007, and who consented to participate in this study. METHODS: We used SD-OCT to image eyes. Multiple B-scans from each eye were saved and independently graded by 2 graders and the following locations were marked: (1) site where PR thickness began to decline below its baseline, (2) site where PR layer disappeared, and (3) site of the GA margin. These data were processed to calculate the locations of PR losses relative to GA margins and were categorized as (A) bridging across GA margins, (B) entirely within GA margins, or (C) entirely outside GA margins. MAIN OUTCOME MEASURES: Location of PR loss (bridging across GA margins, entirely within GA margins, or entirely outside GA margins) was calculated. Distances from the GA margin were measured for beginning and ending of PR loss. Interobserver agreement was determined for categories of PR loss as well as locations of PR loss relative to the GA margin. RESULTS: We analyzed 500 unique scans. The PR loss occurred most frequently bridging across the GA margin (65% scans), second most frequently entirely inside the GA margin (29% scans), and least frequently entirely outside the GA margin (6% scans). Loss of PR started an average of 61 microm (standard deviation [SD] +/- 235) outside the GA margin, ended an average of 311+/-273 microm inside the GA margin, and spanned an average of 372+/-179 microm. CONCLUSIONS: Relative to GA margins in non-neovascular AMD with GA, SD-OCT provides adequate resolution for quantifying PR loss. It may also serve as a means of tracking disease progression in future interventional trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Zone of retinal vascularization and refractive error in premature eyes with and without spontaneously regressed retinopathy of prematurity.

PURPOSE: To evaluate the relationship between zone of retinal vascularization and refractive error in premature infants without retinopathy of prematurity (ROP) or with spontaneously regressed ROP. METHODS: The medical records of neonates screened for ROP between 2009 and 2015 at a tertiary academic center were reviewed retrospectively. Cases included untreated eyes with spontaneously regressed ROP; premature eyes without a diagnosis of ROP were control subjects. Primary outcomes were zone of retinal vascularization and refractive error, determined by cycloplegic retinoscopy (CR). RESULTS: Of 378 eyes evaluated, 184 had ROP, 24 of which underwent treatment and were excluded. Mean corrected age at first CR was 7.5 months. Seventeen eyes without ROP were myopic at first CR (8.8%), compared to 35 eyes with regressed ROP (21.9%). No untreated eyes had halted vasculature in zone I; notably, 44% of spontaneously regressed zone II eyes were myopic. Irrespective of ROP status, CR significantly differed by zone of vascularization (P < 0.001), with more myopia occurring with posterior halting of vascularization. For all eyes, CR significantly differed between complete vascularization versus zone II (P < 0.0001) and zone III versus zone II (P = 0.001); zone III versus complete vascularization did not statistically differ (P = 0.15). This relationship held true for untreated, spontaneously regressed ROP eyes (P < 0.01, P = 0.01, P = 0.8343). CONCLUSIONS: More myopic refraction occurred in neonates screened for ROP with posterior halting of vascularization. Patients with halted vascular growth in zone II should be closely monitored for myopia and refractive amblyopia.

Feasibility of Intraocular Projection for Treatment of Intractable Corneal Opacity.

Despite many decades of research and development, corneal opacity remains a leading cause of reversible blindness worldwide. Corneal transplantation and keratoprosthesis can restore corneal clarity, but both have well-known limitations. High-resolution electronic microdisplays may offer an alternative to traditional methods of treating corneal disease using an intraocular implant to project imagery onto the retina, obviating the need for a clear cornea. In this study, we review previous work and recent technologic developments relevant to the development of such an intraocular projection system.

Early Diagnosis and Management of Aggressive Posterior Vitreoretinopathy Presenting in Premature Neonates.

BACKGROUND AND OBJECTIVE: Aggressive posterior vitreoretinopathy (APVR) manifests with a broad area of retinal avascularity, progressive neovascularization, and/or tractional retinal detachment during the neonatal period. PATIENTS AND METHODS: A multicenter, retrospective, observational, consecutive case series study was performed to evaluate the retinal findings and structural retinal outcomes in patients treated for APVR within the first 3 months of life. RESULTS: Three premature neonates with a non-retinopathy of prematurity (ROP) APVR identified during routine ROP screening exams exhibited relatively severe, rapidly progressive retinal vascular abnormalities. Immediate laser photocoagulation of the avascular retina and vitrectomy for traction retinal detachment within several days to weeks improved or stabilized the retinal anatomy in all cases. CONCLUSIONS: This series describes clinical features in APVR in premature infants and suggests that early diagnosis and intervention may mitigate the typical aggressive course and poor prognosis of this condition. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:201-207.].

Longitudinal Examination of Fellow-Eye Vascular Anomalies in Coats' Disease With Widefield Fluorescein Angiography: A Multicenter Study.

BACKGROUND AND OBJECTIVE: Retinovascular anomalies in the fellow eyes of patients with Coats' disease have been described, but the clinical significance is unknown, as well as whether these lesions progress over time. PATIENTS AND METHODS: This is an international, multicenter, retrospective, observational cohort study of fellow-eye abnormalities on widefield fluorescein angiography in patients with Coats' disease. RESULTS: Three hundred fifty eyes of 175 patients with Coats' disease were analyzed. A total of 33 patients (18.8%) demonstrated abnormal fellow-eye findings: 14 (42.4%) telangiectasias, 18 (54.5%) aneurysms, six (18.2%) segmental non-perfusion, six (18.2%) leakage, and two (6.0%) vascular tortuosity. All eyes were asymptomatic, and none of the lesions progressed over time. There was no association between fellow-eye findings with severity of Coats' disease (P = .16), patient age (P = .16), or presence of systemic vascular disease (P = .16). CONCLUSIONS: The vascular abnormalities in fellow eyes of patients with Coats' disease did not progress over time. Observation is a reasonable initial management strategy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:221-227.].

Surgical Management of an Externally Protruding, Perforating Intraocular Foreign Body.

Ru-ik Chee Felix Y. Chau In this case of a perforating eye injury by a 2-inch-long nail that went through the cornea, lens, and posterior eye wall, the authors describe a combined external, anterior, and posterior segment surgical approach that resulted in safe and successful removal of the foreign body. Initial external trimming of the protruding nail facilitated the use of a noncontact viewing system. Combined limbal and pars plana placement of the vitrectomy cannulas optimized access to both anterior and posterior intraocular structures. Most importantly, careful removal of potential sources of foreign body adhesion to intraocular structures prior to extraction likely increased the likelihood for a successful clinical outcome. Care was taken to remove as much of the vitreous as possible and to keep the eye formed. The patient recovered 20/25+2 vision with aphakic correction.