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Author(s): Bonnet, Clemence; Miller, Kevin M | Abstract: PurposeTo assess the preliminary safety and efficacy of custom silicone artificial iris implantation.SettingStein Eye Institute.DesignProspective consecutive case series.MethodsMedical records of patients implanted with the artificial iris were reviewed and followed for 1 year. Safety measures included corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell count (ECC), surgical complications, secondary interventions, and adverse events (AEs). Efficacy measures included CDVA with glare, subjective daytime and nighttime glare graded from 0 to 10 (very significant), and subjective cosmetic appearance graded from 0 to 10 (very satisfied).ResultsTwenty eyes (19 patients) were implanted. Safety data were mixed. CDVA improved in 13 eyes and worsened in 6. ECC decreased from 1918 ± 870 to 1405 ± 705 cells/mm (P = .02). Eight eyes experienced postoperative complications. There were 4 IOP elevations, 2 corneal decompensations, 1 case of cystoid macular edema, and 1 device dislocation. Four eyes underwent secondary surgical interventions including 2 AEs (1 glaucoma surgery and 1 device dislocation). Efficacy outcomes were excellent. CDVA with glare improved from 1.5 ± 0.6 to 0.7 ± 0.8 logarithm of the minimum angle of resolution (P l .01). Mean subjective daytime glare decreased from 8.9 ± 1.8 to 2.7 ± 2.6 (P l .01) and nighttime glare decreased from 7.9 ± 1.8 to 2.5 ± 2.7 (P l .01). Mean cosmesis improved from 2.2 ± 1.6 to 8.8 ± 2.1 (P l .01).ConclusionsCustom artificial iris implantation was moderately risky but very effective at reducing light and glare sensitivity and in improving ocular cosmesis.

Background Anterior segment optical coherence tomography (AS OCT) is a helpful tool used to diagnose and manage many corneal conditions, but its use has not been reported in case of peripheral ulcerative keratitis (PUK). The aim of this study is to describe AS OCT findings in cases of PUK. Methods Retrospective observational case series of six eyes presenting with a PUK and proven systemic vasculitis. Clinical course, slit lamp photographs, and AS OCT findings were the main outcomes. Results The AS OCT findings were found to correlate with the ocular disease’s level of activity. In the acute stage, an absence of corneal epithelium, a scrambled appearance of the anterior stroma and a heterogeneous stromal reflectivity were observed. During the reduction of disease level activity, an irregular hyporeflective epithelium, a smoother anterior stroma, and a homogenous hyperreflective stroma were seen. At the healed stage, a filling of the corneal defect by a hyporeflective thick epithelium, the persistence of the hyperreflective underlying stroma, and a demarcation line were observed. The mean total corneal thickness at last follow-up was significantly thicker (509 ± 147 μm) compared with the mean corneal thickness at onset (408 ± 131 μm; P = 0.03). Conclusions AS OCT provides an assessment of structural changes occurring in PUK, useful for its diagnosis and monitoring.

Background: This study aimed to assess the diagnostic relevance of CD4/CD8 ratio in cerebrospinal fluid (CSF) for the etiological diagnosis work-up of uveitis.Methods: We consecutively included pat...

Aims To evaluate the clinical and visual outcomes of fluid-filled scleral lens devices (SL) wear in patients with limbal stem cell deficiency (LSCD). Design Retrospective consecutive case series. Methods 27 eyes with LSCD confirmed by in vivo confocal microscopy at the Stein Eye Institute and fitted with SL were included. Correlations between corrected distance visual acuity (CDVA) and LSCD stage determined by clinical grading were performed between baseline (after the SL fit) and the last follow-up (the time of discontinuation of SL wear or the last visit in eyes in which SL were continued). In a subset of patients that had worsened LSCD while using SL, anterior segment optical coherence tomography (AS-OCT) and anterior segment fluorescein angiogram (AS-FA) were performed. Results Baseline LSCD grading was stage I in 12 eyes (44.4%), stage 2 in 12 eyes (44.4%), and stage III in 3 eyes (11.1%). At the last follow-up, CDVA was improved in 7 eyes (25.9%), remained stable in 13 eyes (48.1%) and decreased in 7 eyes (25.9%, P = 0.16). The LSCD stage was improved in 7 eyes (25.9%), remained stable in 8 eyes (29.6%) and worsened in 12 eyes (44.4%, P = 0.10). AS-OCT and AS-FA, performed in 5 eyes, showed limbal compression and delayed fluorescein filling. Conclusion SL can improve visual acuity and maintain the ocular surface in the majority of eyes. Worsening of the ocular surface might be a result of limbal hypoxia. Close monitoring of SL fit is necessary in these compromised eyes.

Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration and remodeling in adults. While aberrant Wnt signaling contributes to diseases such as cancer, activation of Wnt/β-catenin signaling is a target of interest in stem cell therapy and regenerative medicine. Recent high throughput screenings from chemical and biological libraries, combined with improved gene expression reporter assays of Wnt/β-catenin activation together with rational drug design, led to the development of a myriad of Wnt activators, with different mechanisms of actions. Among them, Wnt mimics, antibodies targeting Wnt inhibitors, glycogen-synthase-3β inhibitors, and indirubins and other natural product derivatives are emerging modalities to treat bone, neurodegenerative, eye, and metabolic disorders, as well as prevent ageing. Nevertheless, the creation of Wnt-based therapies has been hampered by challenges in developing potent and selective Wnt activators without off-target effects, such as oncogenesis. On the other hand, to avoid these risks, their use to promote ex vivo expansion during tissue engineering is a promising application., Overview of the Wnt signaling pathway and targets of Wnt activators.

The corneal epithelium is consistently regenerated by limbal stem/progenitor cells (LSCs), a very small population of adult stem cells residing in the limbus. Several Wnt ligands, including Wnt6, are preferentially expressed in the limbus. To investigate the role of Wnt6 in regulating proliferation and maintenance of human LSCs in an in vitro LSC expansion setting, we generated NIH-3T3 feeder cells to overexpress different levels of Wnt6. Characterization of LSCs cultured on Wnt6 expressing 3T3 cells showed that high level of Wnt6 increased proliferation of LSCs. Medium and high levels of Wnt6 also increased the percentage of small cells (diameter ≤ 12 µm), a feature of the stem cell population. Additionally, the percentage of cells expressing the differentiation marker K12 was significantly reduced in the presence of medium and high Wnt6 levels. Although Wnt6 is mostly known as a canonical Wnt ligand, our data showed that canonical and non-canonical Wnt signaling pathways were activated in the Wnt6-supplemented LSC cultures, a finding suggesting that interrelationships between both pathways are required for LSC regulation.

PURPOSE To identify the incidence, risk factors, and outcomes of infectious keratitis after Boston type 1 keratoprosthesis (kpro) implantation. METHODS Retrospective case series of kpro procedures at the Stein Eye Institute and the Centre Hospitalier de l'Universite de Montreal between May 1, 2004, and December 31, 2018. Data were collected regarding ocular history, operative details, postoperative management, microbiologic profile, treatment, and outcomes. Log-rank test and Cox proportional hazard ratio (HR) were used to evaluate for an association between risk factors and outcomes. RESULTS A total of 349 kpro procedures were performed in 295 eyes of 268 patients. Fifty-seven cases of presumed infectious keratitis were identified after 53 procedures (15.2%) in 50 eyes (16.9%) of 49 patients (18.3%). The incidences of culture-positive bacterial and fungal keratitis were 0.014 and 0.004 per eye-year, respectively. Persistent corneal epithelial defect formation (P < 0.001) and cicatricial disease (HR: 1.98, 95% confidence interval, 1.02-3.83) were associated with a significantly higher incidence of infectious keratitis. For the 53 cases with a known outcome, medical therapy achieved resolution of infection in 34 cases (64.2%), whereas kpro explantation was required in 19 cases (35.8%). Infectious keratitis was associated with an increased risk for kpro explantation (HR: 3.09, 95% confidence interval, 1.92-4.79). CONCLUSIONS Infectious keratitis develops in approximately 17% of eyes after kpro implantation, with a higher rate of culture-positive bacterial than fungal keratitis. The observed rate of microbial keratitis suggests the need for additional topical antimicrobial prophylaxis in eyes at higher risk, such as those with preexisting cicatricial disease or postoperative persistent corneal epithelial defect formation.

Author(s): Bonnet, Clemence; Vazirnia, Parsia; Deng, Sophie X; Aldave, Anthony J; Miller, Kevin M | Abstract: PurposeTo assess safety and efficacy outcomes of sutured custom silicone artificial iris and intraocular lens implantation combined with penetrating keratoplasty (triple procedure).MethodsProspective consecutive surgical case series of patients who underwent the triple procedure between 2010 and 2019 at Stein Eye Institute, UCLA, followed up for 1 year minimum. Safety outcomes were changes from preoperative to last follow-up in corrected distance visual acuity (CDVA), endothelial cell count, intraocular pressure (IOP), and postoperative complications. Efficacy outcomes included changes in subjective glare (none to severe), cosmetic appearance (worse to very much improved), and visual function as assessed by the Visual Function Questionnaire-25 at 1-year follow-up.ResultsAmong 82 eyes implanted with an artificial iris, 14 eyes (17.1%) underwent the triple procedure. The median follow-up was 18.1 months (range 12.0-54.9 months). The median CDVA improved from 2.0 log of minimum angle of resolution (logMAR) (range 0.9-2.3 logMAR) to 0.7 logMAR (range 0.2-2.6 logMAR) (P = 0.02). Average endothelial cell count decreased 57.6% (P l 0.01). Six eyes (42.9%) experienced IOP elevations, 13 eyes (92.3%) developed iritis, and 11 eyes (78.6%) underwent secondary surgery. Graft rejection or secondary graft failure occurred in 7 eyes each (50.0%). Cosmesis improved in 12 eyes (85.7%; P l 0.01). The Visual Function Questionnaire-25 score improved from 72 to 77 (P l 0.01). Glare symptoms did not change significantly.ConclusionsThe triple procedure was effective at improving CDVA, cosmesis, and quality of life; however, it was associated with frequent postoperative complications, of which iritis, IOP elevation, and secondary graft failure were the most common.

To determine incidence, risks factors for, and outcomes of idiopathic vitritis (IV) after Boston type 1 keratoprosthesis (KPro) implantation.Retrospective, consecutive case series. Risk factors were analyzed between IV group and No IV group.IV occurred in 32/350 procedures (9.1%), for an average incidence of 0.02 cases per procedure-year. Presumed infectious keratitis was the only risk factor identified (HR = 7.65) Corneal necrosis and retinal detachment occurred significantly more frequently in IV group (allIV is associated with infectious keratitis, indicating that the vitritis may not be a sterile process. The increased incidence of subsequent complications leads to significantly decreased visual acuity and KPro retention in affected eyes.

Cataract is a leading cause of blindness in the world, and cataract extraction is one of the most commonly performed surgeries. Preferred surgical techniques have changed over the past decades with associated improvements in outcomes and safety. Phacoemulsification is a highly successful technique first introduced over 40 years ago. It is the current method of cataract surgery, with a very low reported rate of major complications and a frequency of overall intraoperative complications of less than 2%. Application of the femtosecond laser evolved to now assist in cataract surgery and has been termed FLACS (femtosecond laser-assisted cataract surgery) and occurs in three steps: corneal incisions (including optional limbal relaxing incisions to reduce astigmatism), anterior capsulotomy, and lens fragmentation. The remaining surgical steps still require the surgeon’s hands. The FLACS technique may have some advantages compared with conventional phacoemulsification. It remains however unclear whether FLACS is globally more efficient and safer than conventional surgery. The popularity of FLACS may also be limited by its higher cost compared with conventional surgery. The potential advantages of laser-assisted surgery are yet to be determined as FLACS technology is relatively new and in continuous evolution. This chapter reports scientific data as well as our own experience with this new technology. All the platforms currently available are described.

Purpose To describe the causes and prevalence of moderate-to-severe visual impairment (MSVI) and blindness from corneal diseases, as well as corneal transplantation across Asia. Methods A meta-analysis of the published literature to identify population-based surveys conducted from 2008 to 2019 in 22 Asian countries regarding the prevalence and causes of MSVI and blindness from corneal disease, and a review of national corneal transplant data and eye bank statistics. Results A total of 5307 records were screened to identify 57 reports that were used to estimate a prevalence of MSVI and blindness caused by corneal diseases in Asia of 0.38% (95% confidence interval, 0.29%-0.48%). The most frequent corneal diseases were infectious keratitis, trauma, and pseudophakic bullous keratopathy. As expected, these represented the most common indications for corneal transplantation, although the percentages in each country differed based on the level of economic development, with pseudophakic bullous keratopathy being the most common indication in countries with higher gross national income per capita. Despite this, endothelial keratoplasty is not the most commonly performed form of corneal transplantation in any Asian country and represents only a small percentage of keratoplasty procedures performed in most countries. Conclusions The prevalence of MSVI and blindness from corneal disease in Asia is approximately 0.4%, with a nearly 20-fold difference in the national prevalence across the region. The indications for keratoplasty, reflective of the causes of corneal dysfunction, also vary, more so according to the gross national income than to geographic location, and only a few Asian countries have rates of corneal transplantation above international means.

Purpose To investigate the presence of pre-Descemet corneal dystrophy (PDCD) in association with X-linked ichthyosis (XLI) in an 11-year-old boy using multimodal imaging and genetic analysis. Methods Corneal opacities were examined and imaged with slit-lamp biomicroscopy, anterior segment optical coherence tomography, noncontact specular microscopy, and in vivo confocal microscopy. Cytogenomic array analysis was performed using genomic DNA isolated from the patient. Results Corneal opacities characteristic of PDCD located in the posterior corneal stroma just anterior to Descemet membrane were identified by slit-lamp biomicroscopy. A pre-Descemet hyper-reflective line, consistent with these opacities, was seen with anterior segment optical coherence tomography. Scheimpflug tomography revealed a bimodal peak light scattering. In vivo confocal microscopy findings were unremarkable. Copy number analysis identified a 4389 kbp hemizygous deletion on the X chromosome (chr. X: 6,540,898-8,167,604), resulting in the deletion of 4 genes, including the known locus of XLI, the STS gene. Conclusions This report demonstrates that PDCD-associated XLI may present in children and that the diagnosis may be confirmed through multimodal imaging in conjunction with genetic analysis.

Purpose Iris intraocular implants were developed to manage congenital or traumatic iris defects. However, they are also used to change the color of patient eyes. The aim of this retrospective series was to report complications in patients managed in France after cosmetic implantation. Setting Ophthalmological institutions and private ophthalmologists in France. Design Multicenter retrospective observational study. Methods Questionnaires were sent to all ophthalmology departments in university hospitals and to private ophthalmologists. This questionnaire listed demographic and clinical data for each implanted eye with a focus on safety, the description of ocular complications (corneal edema, endothelial cell loss, increased intraocular pressure, and intraocular inflammation), and the therapeutic management implemented. Results Forty-four questionnaires (87 eyes) were collected, and ultimately, 33 questionnaires (65 eyes) were considered complete and analyzed. Two types of implants were identified. Of the 65 eyes analyzed, only 5 eyes (7.7%) did not experience any complication and 60 eyes (92.3%) had at least 1 complication. The most commonly reported complication was corneal decompensation (78.5%). The diagnosis of glaucoma was made in over half (52.3%) of the cases. Explantation was needed in 81.5% of cases. The mean final visual acuity was 0.45 ± 0.08 logarithm of the minimum angle of resolution (logMAR) (0 to 2 logMAR). Conclusions Several ocular complications with a decreased mean visual acuity were described in a young healthy population. In addition, patient information on the safety of this procedure appeared insufficient.

The purpose of this study was to evaluate the long-term outcomes of Descemet membrane endothelial keratoplasty (DMEK) in eyes that had previously undergone trabeculectomy and/or drainage device implantation.Retrospective, noncomparative case series.Medical records of 251 consecutive DMEK procedures performed by 1 surgeon (S.X.D.) from 2013 to 2017 were reviewed. Patients with ≥2 years of follow-up were divided into 3 groups: eyes with prior glaucoma surgery (ST), eyes with medically treated glaucoma (MT), and eyes without glaucoma (NG). Main outcomes measured were visual acuity, endothelial cell count (ECC), rates of secondary graft failure (SGF), and postoperative complications.Ninety procedures (87 eyes) met inclusion criteria. The mean follow-up period of all eyes was 38.4 ± 11.2 months (range, 24.2-64.4 months). At last follow-up, the proportion of eyes reaching a vision of ≥20/40 was higher than that before the DMEK procedure in each group (all P.05). The rate of ECC loss was the highest in the ST group compared to that in the MT and NG groups (63.8% vs 47.6% vs 44.0%, respectively; P.05) as well as the rate of SGF (41.6% vs 0% vs 2.4%, respectively; P.05). The rate of SGF of repeat DMEK was higher than that of primary DMEK (P.05). The rates of postoperative complications were similar among all groups (all P.05).In eyes with prior glaucoma surgery, DMEK achieved good long-term visual outcomes but experienced a higher rate of SGF than eyes without such comorbidity.

Background: Anterior-segment optical coherence tomography (AS-OCT) is an important tool, helpful to diagnose and manage many corneal conditions, but has not been reported in cases of peripheral ulcerative keratitis (PUK). The aim of this study is to describe AS-OCT findingsin cases of PUK.Methods: Retrospective observational case series of six eyes with a PUK with proven systemic vasculitis. Clinical course, slit-lamp photographs, and AS-OCT findings were the main outcomes.Results: The AS-OCT findings were found to correlate with the ocular disease’s level of activity. In the acute stage, an absence of corneal epithelium, a scrambled appearance of the anterior stroma and a heterogeneous stromal reflectivity were observed. During the reduction of disease level activity, an irregular hyporeflective epithelium, a smoother anterior stroma, and a homogenous hyperreflective stroma were seen. At the healed stage, a filling of the corneal defect by a hyporeflective thick epithelium, the persistence of the hyperreflective underlying stroma, and a demarcation line were observed.Conclusions: AS-OCT provides an assessment of structural changes occurring in PUK, useful for its diagnosis and monitoring.

The corneal epithelium is continuously renewed by limbal stem/progenitor cells (LSCs), a cell population harbored in a highly regulated niche located at the limbus. Dysfunction and/or loss of LSCs and their niche cause limbal stem cell deficiency (LSCD), a disease that is marked by invasion of conjunctival epithelium into the cornea and results in failure of epithelial wound healing. Corneal opacity, pain, loss of vision, and blindness are the consequences of LSCD. Successful treatment of LSCD depends on accurate diagnosis and staging of the disease and requires restoration of functional LSCs and their niche. This review highlights the major advances in the identification of potential LSC biomarkers and components of the LSC niche, understanding of LSC regulation, methods and regulatory standards in bioengineering of LSCs, and diagnosis and staging of LSCD. Overall, this review presents key points for researchers and clinicians alike to consider in deepening the understanding of LSC biology and improving LSCD therapies.

The function of limbal stem/progenitor cells (LSCs) is critical to maintain corneal epithelial homeostasis. Many external insults and intrinsic defects can be deleterious to LSCs and their niche microenvironment, resulting in limbal stem cell dysfunction or deficiency (LSCD). Ocular comorbidities, frequent in eyes with LSCD, can exacerbate the dysfunction of residual LSCs, and limit the survival of transplanted LSCs. Clinical presentation and disease evolution vary among different etiologies of LSCD. New ocular imaging modalities and molecular markers are now available to standardize the diagnosis criteria and stage the severity of the disease. Medical therapies may be sufficient to reverse the disease if residual LSCs are present. A stepwise approach should be followed to optimize the ocular surface, eliminate the causative factors and treat comorbid conditions, before considering surgical interventions. Furthermore, surgical options are selected depending on the severity and laterality of the disease. The standardized diagnostic criteria to stage the disease is necessary to objectively evaluate and compare the efficacy of the emerging customized therapies.

Purpose: We observed hyperreflective dome-shaped or pyramidal structures (HPS) on spectral domain optical coherence tomography (SD-OCT) in patients affected with geographic atrophy (GA). Our purpose was to describe the multimodal imaging features of HPS identified in areas of GA in patients with age-related macular degeneration. Methods: This is a retrospective case series of patients with GA harboring HPS in atrophic areas. Multimodal imaging examination including infrared reflectance, fundus autofluorescence, and SD-OCT, was performed for each patient. Infrared and fundus autofluorescence appearance and mean SD-OCT height of HPS in GA were analyzed. Results: A total of 36 eyes of 25 patients (20 women; mean age, 82.3 +/- 5.9 years, range, 73-92 years) with GA were included. A total of 96 HPS in GA were analyzed by SD-OCT. In all HPS (96/96, 100%), the peripheral part was hyperreflective. In 66 of 96 HPS (69%), the center was heterogeneously hyperreflective, whereas in 30 of 96 HPS (31%), the center was hyporeflective. On infrared reflectance images, HPS in GA appeared as hyporeflective lesions surrounded by hyperreflective halos, within an area of background hyperreflectivity because of GA in all eyes. On fundus autofluorescence, 39 of 96 HPS (41%) were heterogeneously hyperautofluorescent, whereas 57 of 96 HPS (59%) were hypoautofluorescent. Mean height of HPS was 91 +/- 50.9 mu m in the foveal scan (range, 42-291 mu m). Conclusion: We describe a multimodal imaging of distinctive lesions that presented as hyperreflective pyramidal structures on SD-OCT. We suggest the name "ghost drusen" because these HPS appear in GA areas, and because of their pyramidal or dome-shaped aspect on SD-OCT.

Purpose To report long-term results of Artisan phakic intraocular lens (pIOL) to correct myopia and to propose a model predicting endothelial cell loss after pIOL implantation. Setting Quinze-Vingts National Ophthalmology Hospital, Paris, France. Design Retrospective, interventional case series. Methods Uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and central endothelial cell count (ECC) were determined before and at yearly intervals up to 5 years after pIOL implantation. Linear model analysis was performed to present a model that describes endothelial cell loss as a linear decrease and an additional decrease depending on postoperative loss. Results A total of 49 patients (68 eyes) implanted with pIOLs from January 2000 to January 2009 were evaluated. The mean preoperative and final spherical equivalent (SE) were −13 ± 4.10 and −0.75 ± 0.74 diopters (D), respectively. The mean preoperative and final central ECC were 2629 ± 366 and 2250 ± 454 cells/mm 2 , respectively. There were no intraoperative complications for any of the eyes. One eye required surgery for repositioning the pIOL, and 1 eye required pIOL exchange for postoperative refractive error. The model predicted that for patients with preoperative ECC of 3000, 2500, and 2000 cells/mm 2 , a critical ECC of 1500 cells/mm 2 will be reached at 39, 28, and 15 years after implantation, respectively. Conclusions Implantation of the pIOL was an effective and stable procedure after 5 years of follow-up. The presented model predicted EC loss after pIOL implantation, which can assist ophthalmologists in patient selection and follow-up. Financial disclosure The authors report no conflict of interest.

Purpose To analyze specific outer retinal and retinal pigment epithelium (RPE) features in reticular pattern dystrophy using spectral-domain optical coherence tomography (SD-OCT). Methods Consecutive patients with reticular pattern dystrophy underwent a complete ophthalmologic examination, including assessment of best-corrected visual acuity (BCVA), fundus biomicroscopy, and SD-OCT (Spectralis SD-OCT, Heidelberg Engineering). Outer retinal and RPE macular features, as evaluated by SD-OCT (scan passing through the fovea) were analyzed by 3 authors (JZ, NM and GQ). Results 24 eyes of 13 patients (5 males, 8 women, mean age 71.4) were included. Mean visual acuity was measured at 0.30 (logMAR). The RPE layer in the foveal area appeared normal in 41.7% of scans, while small RPE elevations and RPE bumps were detected in 33.3% and 20.8% of scans, respectively. Inner segment/outer segment (IS/OS) junction appeared disrupted in 50% of scans, and absent in 58.3% of scans. SD-OCT showed a slight IS/OS elevation in 54.2% of scans. The external limiting membrane (ELM), appeared disrupted in 50% of scans, absent in 37.5% of scans, and elevated in 66.7% of scans. Hypereflective subretinal material accumulation or hyporeflective subretinal lesions, were detected in 33.3% and in 12.5% of scans, respectively. SD-OCT showed hyporeflective retinal pseudocysts in 16.7% of scans. Conclusion In this series of reticular pattern dystrophy, SD-OCT showed disruption of RPE layer and RPE bumps. Outer retinal changes included absence and disruption of both IS/OS junction and ELM. Hypereflective subretinal material accumulation or hyporeflective subretinal lesions, and hyporeflective retinal pseudocysts were also noticed.