VALUE OF FRACTAL ANALYSIS OF OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN VARIOUS STAGES OF DIABETIC RETINOPATHY.

PURPOSE: To use fractal dimensional analysis to investigate retinal vascular disease patterns in patients with diabetic retinopathy using spectral domain optical coherence tomography angiography. METHODS: A retrospective study was conducted which included 49 eyes from 26 control subjects and 58 eyes from 35 patients known to have diabetic retinopathy. Of the 58 eyes with known retinopathy, 31 were categorized as nonproliferative diabetic retinopathy (13 mild, 9 moderate, and 9 severe) and 27 were categorized as proliferative diabetic retinopathy. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti (Optovue, Inc). Automated segmentation was obtained through both the superficial and deep capillary plexuses for each eye. Grayscale optical coherence tomography angiography images were standardized and binarized using ImageJ (National Institutes of Health). Fractal box-counting analyses were conducted using Fractalyse (ThéMA). Fractal dimensions (FDs) and correlation coefficient of the superficial and deep capillary plexuses were compared between control eyes and those in various stages of diabetic retinopathy. RESULTS: The superficial and deep capillary plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than in control eyes in the superficial plexus (P = 2.4 × 10) and in the deep capillary plexus (P = 1.87 × 10 ) with a more statistically significant difference noted in the deep capillary plexus. When analyzing diabetic patients without edema noted on optical coherence tomography, the FD was significantly reduced in the superficial (P = 0.001) and deep (P = 1.49 × 10) plexuses. When analyzing diabetic patients with edema noted on optical coherence tomography, the FD was significantly reduced in the superficial (P = 2.0 × 10) and deep (P = 1.85 × 10) plexuses. CONCLUSION: The optical coherence tomography angiography FD is significantly lower in both superficial and deep capillary plexuses in eyes with all stages studied of diabetic retinopathy. The results were more often significant for the deep capillary plexus. The use of fractal analysis provides an objective criterion to assess microvascular disease burden in diabetic retinopathy.

The Current State of Teleophthalmology in the United States.

Telemedicine services facilitate the evaluation, diagnosis, and management of the remote patient. Telemedicine has rapidly flourished in the United States and has improved access to care, outcomes, and patient satisfaction. However, the use of telemedicine in ophthalmology is currently in its infancy and has yet to gain wide acceptance. Current models of telemedicine in ophthalmology are largely performed via "store and forward" methods, but remote monitoring and interactive modalities exist. Although studies have examined the effects of telemedicine, few reports have characterized its current status. We perform a descriptive analysis of the current state of teleophthalmology in the United States. We describe the use of teleophthalmology in the hospital and outpatient settings. We also review the applications to retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and glaucoma, as well as anticipated barriers and hurdles for the future adoption of teleophthalmology. With ongoing advances in teleophthalmology, these models may provide earlier detection and more reliable monitoring of vision-threatening diseases.

FOVEAL EXUDATE AND CHOROIDAL NEOVASCULARIZATION IN ATYPICAL CASES OF MULTIPLE EVANESCENT WHITE DOT SYNDROME.

PURPOSE: To describe atypical cases of multiple evanescent white dot syndrome (MEWDS) associated with foveal exudation, increased choroidal thickness, and secondary Type 2 (subretinal) neovascularization. METHODS: Four cases of atypical MEWDS were studied at a retina referral center. Patients underwent evaluation with multimodal retinal imaging, including fluorescein angiography, indocyanine green angiography, spectral-domain and enhanced depth imaging optical coherence tomography (OCT). Two patients were imaged with OCT angiography. RESULTS: Four patients (3 female, 1 male) with a median age of 23.5 years presented with acute onset, painless, decreased central vision. All cases demonstrated fundus findings consistent with MEWDS on color photography, indocyanine green angiography, fluorescein angiography, fundus autofluorescence, and structural OCT imaging. On structural OCT, all 4 patients were noted to have hyperreflective subretinal material and increased subfoveal choroidal thickness ranging from 307 µm to 515 µm. Type 2 neovascularization was diagnosed in all four patients using fluorescein angiography, indocyanine green angiography, and/or OCT angiography. Two patients had poor visual acuity at the last follow-up despite resolution of characteristic clinical findings of MEWDS. CONCLUSION: A subset of patients with atypical MEWDS may develop persistent poor vision due to subfoveal exudation and secondary Type 2 neovascularization. Patients showing increased choroidal thickness at presentation may be more susceptible to this unusual presentation.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF CHORIORETINAL LESIONS DUE TO IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To evaluate the spectrum of macular chorioretinal lesions occurring in idiopathic multifocal choroiditis using optical coherence tomography angiography (OCTA) to evaluate those showing neovascular flow. METHODS: This was a descriptive, retrospective study of 18 eyes of 14 patients with multifocal choroiditis. Macular lesions were characterized as subretinal pigment epithelium, subretinal, or mixed and evaluated during active and presumed inactive states of multifocal choroiditis. Correlations between structural optical coherence tomography and OCTA were performed. In select cases, correlations between OCTA, fluorescein angiography, and fundus autofluorescence were evaluated. In 5 eyes, quantitative measurements of neovascular lesions were compared at baseline and following intravitreal anti-vascular endothelial growth factor therapy. RESULTS: Mean patient age was 48 years (SD: 13.8; 86% women). Optical coherence tomography angiography flow signatures consistent with neovascularization were identified in 83% of eyes, including in 0% of subretinal pigment epithelium, 91% of subretinal, and 100% of mixed lesions. Lesions that did not demonstrate definitive signs of fluorescein angiography leakage were frequently found to have neovascularization using OCTA. There was no change in quantitative measurements of neovascular lesions after anti-vascular endothelial growth factor therapy (all tested variables P > 0.05). CONCLUSION: Optical coherence tomography angiography may be a useful imaging modality for understanding the pathophysiology of multifocal choroiditis and monitoring its clinical course.

Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration.

The adult mouse prostate has a seemingly endless capacity for regeneration, and sonic hedgehog (SHH) signaling has been implicated in this stem cell-driven process. However, it is not clear whether SHH acts on the epithelium or stromal cells that secrete factors required for epithelial expansion. Because little is known about stromal stem cells compared with their epithelial counterparts, we used in vivo mouse genetics tools to characterize four prostate stromal subtypes and their stem cells. Using knockin reporter alleles, we uncovered that SHH signals from prostate basal epithelial cells to adjacent stromal cells. Furthermore, the SHH target gene Gli1 is preferentially expressed in subepithelial fibroblast-like cells, one of four prostate stromal subtypes and the subtype closest to the epithelial source of SHH. Using Genetic Inducible Fate Mapping to mark adult Gli1- or Smooth muscle actin-expressing cells and follow their fate during regeneration, we uncovered that Gli1-expressing cells exhibit long-term self-renewal capacity during multiple rounds of androgen-mediated regeneration after castration-induced involution, and depleted smooth muscle cells are mainly replenished by preexisting smooth muscle cells. Based on our Genetic Inducible Fate Mapping studies, we propose a model where SHH signals to multiple stromal stem cells, which are largely unipotent in vivo.

Vision Loss After Central Retinal Artery Occlusion Secondary to Orbital Sarcoid Mass.

The authors describe the first report in the literature of central retinal artery occlusion as the presenting manifestation of sarcoidosis. A 33-year-old man with asthma, headache, and 6 days of intermittent, transient vision loss in the OS presented with persistent vision loss in the OS. Ophthalmic examination was consistent with diagnosis of central retinal artery occlusion in the OS. Vascular imaging with CT angiography revealed an incidental finding of an intraconal mass surrounding the left optic nerve and hilar lymphadenopathy. Broncho scopic lymph node biopsy demonstrated noncaseating granulomas consistent with sarcoidosis. This case proffers a unique mechanism of vision loss in sarcoidosis and highlights that atypical causes of central retinal artery occlusion must be considered in patients without typical risk factors.

Digital quantification of Goldmann visual fields (GVFs) as a means for genotype-phenotype comparisons and detection of progression in retinal degenerations.

PURPOSE: To develop a reliable and efficient digital method to quantify planimetric Goldmann visual field (GVF) data to monitor disease course and treatment responses in retinal degenerative diseases. METHODS: A novel method to digitally quantify GVFs using Adobe Photoshop CS3 was developed for comparison to traditional digital planimetry (Placom 45C digital planimeter; Engineer Supply, Lynchburg, Virginia, USA). GVFs from 20 eyes from 10 patients with Stargardt disease were quantified to assess the difference between the two methods (a total of 230 measurements per method). This quantification approach was also applied to 13 patients with X-linked retinitis pigmentosa (XLRP) with mutations in RPGR. RESULTS: Overall, measurements using Adobe Photoshop were more rapidly performed than those using conventional planimetry. Photoshop measurements also exhibited less inter- and intraobserver variability. GVF areas for the I4e isopter in patients with the same mutation in RPGR who were nearby in age had similar qualitative and quantitative areas. CONCLUSIONS: Quantification of GVFs using Adobe Photoshop is quicker, more reliable, and less user dependent than conventional digital planimetry. It will be a useful tool for both retrospective and prospective studies of disease course as well as for monitoring treatment response in clinical trials for retinal degenerative diseases.

DEVELOPMENT OF CHOROIDAL NEOVASCULARIZATION AFTER TREATMENT WITH PHOTODYNAMIC THERAPY IN A 5-YEAR-OLD FEMALE WITH CHOROIDAL OSTEOMA.

PURPOSE: To describe a patient with a choroidal osteoma treated with photodynamic therapy to prevent tumor growth in whom choroidal neovascularization (CNV) developed after being treated with photodynamic therapy. METHODS: Case report. RESULTS: A 5-year-old Hispanic woman presented with an asymptomatic choroidal osteoma, temporal to the macula of her right eye. According to the patient's mother, her medical, surgical, and family history was unremarkable. At examination, best-corrected visual acuity was 20/30 in both eyes. After 11 months of follow-up, signs of tumor growth toward the fovea without any signs of CNV was noted. Photodynamic therapy was performed to prevent invasion of the foveola. Two months thereafter, the patient developed CNV in the macula region in the right eye, decreasing visual acuity to 20/200. The patient was treated with four total intravitreal injections of 1.25 mg of bevacizumab over 24 weeks, which resulted in inactivation of the CNV and improved visual acuity to 20/20. Choroidal neovascularization had been never reported in her past history and her follow-up visits over 7 years. In addition, no evidence of recurrent neovascular activity or tumor growth was reported. CONCLUSION: Choroidal osteoma is a benign tumor that can result in vision-threatening complications, caused by tumor growth and tumor decalcification. Photodynamic therapy is an effective modality in inducing choroidal osteoma decalcification and stabilization; however, CNV due to reperfusion following photodynamic therapy can be seen in the retina.

APPLICATION OF ADJUNCTIVE TOPICAL MITOMYCIN-C IN SCLEROSTOMY REVISION FOR REFRACTORY IDIOPATHIC UVEAL EFFUSION SYNDROME.

BACKGROUND/PURPOSE: To describe the use of topical mitomycin-C in sclerostomy revision for recalcitrant idiopathic uveal effusion syndrome. METHODS: A 50-year-old healthy man presented with painless, gradual vision loss in the right eye. He underwent multimodal retinal imaging with wide-field fundus photography, spectral domain optical coherence tomography, and B-scan and A-scan ultrasonography. He was found to have idiopathic (non-nanophthalmic) uveal effusion syndrome with choroidal and serous retinal detachments in the right eye and a peripheral choroidal detachment in the left eye. Central vision became threatened in the right eye. Medical treatment with oral corticosteroids and surgical treatment with choroidal drainage through sclerostomies and sclerostomy revision were administered. RESULTS: Initial treatment with systemic corticosteroids was ineffective. Subsequent choroidal drainage through sclerostomies only partially resolved the effusion. Later sclerostomy revision with application of topical mitomycin-C led to complete resolution with anatomical stability maintained after at least 42 months of follow-up. CONCLUSION: Successful use of topical mitomycin-C in sclerostomy revision has not previously been reported in idiopathic (non-nanophthalmic) uveal effusion syndrome. We propose that topical mitomycin-C may be considered as a potential therapeutic adjunct in the treatment of refractory idiopathic uveal effusion syndrome before further sclerostomy procedures are attempted in additional quadrants of the eye.

Simulating vascular leakage on optical coherence tomography angiography using an overlay technique with corresponding thickness maps.

BACKGROUND: To demonstrate a technique for using optical coherence tomography angiography (OCTA) to simulate leakage in eyes with diabetic macular oedema and determine the sensitivity and positive predictive value of detecting leaking microvasculature on OCTA using fluorescein angiography (FA) as the comparative norm. METHODS: 6×6 mm OCT angiograms were overlaid with the corresponding OCT thickness maps. Microvascular abnormalities on the OCT angiogram underlying areas of thickening on the OCT thickness map were assumed to be leaking. Two independent readers blindly read the OCTA overlay images then the FA images cropped to the same approximate region to delineate areas of leaking microvasculature. The results were compared to determine the sensitivity and positive predictive value of OCTA for detection of leaking vessels. RESULTS: 28 eyes of 19 diabetic patients were included. Each eye demonstrated an average of seven leaking microvascular abnormalities on the OCTA images and 22 leaking abnormalities on the FA images. Sensitivity of leaking microvasculature detection by OCTA was 26.1% and positive predictive value was 68.4%. The correlation coefficient of the two readers' detection of leaking microvasculature was 0.605 for OCTA reads compared with 0.916 for FA. CONCLUSION: OCTA as a whole can be used to simulate leakage, but currently, sensitivity of the technique is low. Further understanding of the OCTA technology may yield novel means of detecting retinal pathology.

LONG-TERM FOLLOW-UP OF RETINAL PIGMENT EPITHELIUM RESTORATION AFTER A TRIPLE TEAR.

PURPOSE: To demonstrate longitudinal multimodal imaging findings in a case of neovascular age-related macular degeneration presenting with multiple retinal pigment epithelium (RPE) tears showing progressive RPE restoration. METHODS: Observational clinical case report. RESULTS: A 79-year-old woman diagnosed with neovascular age-related macular degeneration developed 3 consecutive RPE tears in her right eye during the course of treatment with intravitreal anti-vascular endothelial growth factor therapy. The RPE tears initially appeared hypoautofluorescent on fundus autofluorescence. Spectral domain optical coherence tomography showed contractile folds of the RPE with adjacent subretinal fluid and overlying ellipsoid zone disruption. Over an 8-year follow-up period, the RPE defects progressively resolved with a return of patchy fundus autofluorescence. Eye-tracked spectral domain optical coherence tomography showed gradual restoration of the RPE band defects over an enlarging Type 1 neovascular lesion. CONCLUSION: Some RPE tears may show observable remodeling and restoration over time. These changes may be followed longitudinally with multimodal imaging, including eye-tracked spectral domain optical coherence tomography and fundus autofluorescence.

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.].

Repairing DNA damage in xeroderma pigmentosum: T4N5 lotion and gene therapy.

Patients with xeroderma pigmentosum (XP) have defective DNA repair and are at a high risk for cutaneous malignancies. Standard treatments for XP are limited in scope and effectiveness. Understanding the molecular etiology of XP has led to the development of novel therapeutic approaches, including enzyme and gene therapies. One new topical treatment utilizing bacteriophage T4 endonuclease 5 (T4N5) in a liposomal lotion is currently in clinical trials and has received a Fast Track designation from the FDA. Gene therapy for XP, while making leaps in preclinical studies, has been slower to develop due to tactical hurdles, but seems to have much potential for future treatment. If these treatments prove effective in lowering the risk of cancer in patients with XP, they may also be found useful in reducing skin cancers in other at-risk patient populations.

An Assessment of Vitreous Degeneration in Eyes with Vitreomacular Traction and Macular Holes.

Purpose. To compare the stages of vitreous degeneration in patients with vitreomacular traction (VMT) and macular holes (MH). Methods. A retrospective study was performed analyzing stages of vitreous degeneration of eyes with VMT or MH using swept-source optical coherence tomography (SS-OCT) and spectral-domain optical coherence tomography (SD-OCT). An analogous review was performed on a control group of eyes with contralateral posterior vitreous detachments. Thirty-four eyes with VMT/MH and 39 control eyes were reviewed. Results. Twenty-seven VMT/MH eyes and 31 control eyes were included. Eyes with VMT/MH demonstrated significantly earlier stages of vitreous degeneration when compared to the control group (p = 0.048) despite significantly greater age (p = 0.032). Conclusions. Vitreoretinal interface disease is more often associated with a formed vitreous and an intact premacular bursa. This is contrary to previous assumptions implicating degeneration of vitreous as a precipitating factor of interface disease when in conjunction with abnormal vitreomacular separation.

Optical Coherence Tomography Evaluation of Valsalva-Induced Suprachoroidal Hemorrhage.

Suprachoroidal hemorrhage is typically observed in patients with hypotony in the context of intraocular surgery and trauma. We report a rare presentation of suprachoroidal hemorrhage associated with emesis (Valsalva maneuver) in a myopic patient with few other identifiable risk factors. This diagnosis was confirmed with wide-field fundus photography and B-scan ultrasound and was localized to the suprachoroidal space using both enhanced depth and swept-source optical coherence tomography imaging. This case is unique in its presentation and demonstrates the utility of newer imaging techniques to localize hemorrhages using a multimodal approach. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:674-676.].

Fractal Dimensional Analysis of Optical Coherence Tomography Angiography in Eyes With Diabetic Retinopathy.

PURPOSE: We used fractal dimensional analysis to analyze retinal vascular disease burden in eyes with diabetic retinopathy using spectral-domain optical coherence tomography angiography (OCTA). METHODS: A retrospective study was performed of 13 eyes with diabetic retinopathy without diabetic macular edema and 56 control eyes. Optical coherence tomography angiography images were acquired using the RTVue XR Avanti. Automated segmentation was obtained through the superficial and deep capillary plexuses for each eye. Grayscale OCTA images were standardized and binarized using ImageJ. Fractal box-counting analyses were performed using Fractalyse. Fractal dimensions (FD) as well as software-generated vascular density analyses of the superficial and deep capillary plexuses were compared between diabetic and control eyes using 2-tailed t-tests and 1-way multivariate ANOVA (MANOVA) analyses. RESULTS: The superficial and deep plexuses from diabetic and control eyes were analyzed. The average FD for diabetic eyes was significantly lower than control eyes for the superficial (P = 4.513 × 10-3) and deep (P = 2.653 × 10-3) capillary plexuses. In diabetic eyes, the vascular density also was significantly reduced in the superficial (P = 8.068 × 10-5) and deep (P = 3.120 × 10-6) capillary plexuses. One-way MANOVA showed a significant difference between diabetic and control eyes. CONCLUSIONS: The OCTA FD is significantly reduced in the superficial and deep capillary plexuses in eyes with diabetic retinopathy. Applying fractal analysis to OCTA imaging holds the potential to establish quantitative parameters for microvascular pathology.

Risk of endophthalmitis and other long-term complications of trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS).

PURPOSE: To report the risk of endophthalmitis and other long-term complications in patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study. DESIGN: A longitudinal cohort study using data collected from a multicenter, randomized clinical trial. METHODS: Long-term postoperative complications in the 300 patients randomized to trabeculectomy in the Collaborative Initial Glaucoma Treatment Study were tabulated. Kaplan-Meier analyses were used to estimate the time-related probabilities of blebitis, hypotony, and endophthalmitis. RESULTS: Two hundred eighty-five patients were included in the final trabeculectomy cohort after accounting for declining treatment assignment and other early events. Patients were followed up for an average of 7.2 years. One hundred sixty-three patients (57%) received 5-fluorouracil during surgery. Of the 247 patients with at least 5 years of follow-up, 50 required further treatment for glaucoma. Cataract extraction was performed in 57 patients (20%). Forty patients (14%) required bleb revision at least once. Bleb-related complications included bleb leak (n = 15), blebitis (n = 8), and hypotony (n = 4). Three patients were noted to have endophthalmitis, although the diagnosis in 2 patients was presumptive. The occurrences of blebitis, hypotony, or endophthalmitis were not significantly associated with 5-fluorouracil use. The Kaplan-Meier calculated risks of blebitis and hypotony at 5 years were both 1.5%, whereas the risk of endophthalmitis was 1.1%. CONCLUSIONS: The potential efficacy of trabeculectomy must be weighed against the long-term risk of complications, especially endophthalmitis, when selecting treatments for patients with open-angle glaucoma. We report a low 5-year risk of endophthalmitis (1.1%) and other bleb-related complications in the trabeculectomy cohort of the Collaborative Initial Glaucoma Treatment Study.

Autofluorescence quantification of benign and malignant choroidal nevomelanocytic tumors.

IMPORTANCE: Accurate diagnosis of choroidal melanoma is challenging and has important implications for both physicians and patients. We assessed the utility of quantification of fundus autofluorescence in the evaluation and follow-up of choroidal nevomelanocytic tumors. OBJECTIVE: To assess the utility of autofluorescence quantification in distinguishing clinically diagnosed choroidal nevi, melanoma, and indeterminate nevomelanocytic lesions. DESIGN, SETTING, AND PARTICIPANTS: A retrospective observational study from 2006 to 2012 of patients with choroidal nevomelanocytic lesions who had digital autofluorescence and color fundus imaging performed at the University of Michigan Kellogg Eye Center. INTERVENTION: ImageJ software was used to output autofluorescence gray-scale values for each pixel of a 500 × 50-pixel region within each lesion and a corresponding adjacent control region. MAIN OUTCOME AND MEASURE: A single value was generated, termed the Index of Retinal Autofluorescence (IRA), to represent the total difference in gray-scale values between the 2 regions in each affected eye. RESULTS: Thirteen of the 14 clinically diagnosed nevi exhibited an IRA less than 150 gray-scale intensity squared (gsi2). Eight of 9 clinically diagnosed melanomas exhibited an IRA more than 150 gsi2. An IRA of 150 gsi2 distinguished nevi from melanomas with a sensitivity of 0.89 and specificity of 0.93. Fifteen of 19 patients with indeterminate nevomelanocytic lesions underwent clinical assessment and initial imaging with clinical follow-up at a median of 10 months. All 3 patients with an IRA less than 150 gsi2 showed no evidence of clinical progression and 6 of 12 lesions with an IRA more than 150 gsi2 showed clinical progression to melanoma. An IRA of 150 gsi2 identifies indeterminate lesions that progressed to melanoma with a sensitivity of 1.00 and specificity of 0.33. CONCLUSIONS AND RELEVANCE: Quantification of digital autofluorescence images can differentiate between clinically benign and malignant choroidal nevomelanocytic lesions and may be predictive for clinical progression of indeterminate lesions.