Dr. Moshiri’s commitment to academic medicine is founded on his scientific interest in retinal genetics and retinal stem cell biology, and he pursues an active laboratory research program. His research background is in the embryonic development of the retina. Under the supervision of Professor Thomas A. Reh at the University of Washington in Seattle, Dr. Moshiri earned a Ph.D. in Neurobiology studying the genetic control of retinal stem cells during eye development. He applied these studies from the embryonic retina to replace retinal cells after injury in adult animals.
His current research in the laboratory is an extension of the earlier experiments during his Ph.D. studies. Dr. Moshiri is actively involved in the study of how retinal photoreceptors, called rods and cones, function. He also focuses on how to promote the survival of these photoreceptor cells, and how to replace them using stem cells and gene therapy. Dr. Moshiri has a special interest in genetic eye diseases like Retinitis Pigmentosa, Stargardt disease, Albinism, and other related conditions where rods and cones do not function properly. He hopes his research will contribute to novel therapies for these hereditary retinal diseases.
His clinical expertise includes all diseases of the retina, including all forms of Macular Degeneration, Retinal Vascular and Inflammatory diseases, medical and surgical management of Diabetic Retinopathy, and all surgical diseases of the retina, including Macular Hole, Macular Pucker, and Retinal Detachment. Dr. Moshiri particularly enjoys seeing patients with difficult-to-diagnose or rare conditions that have eluded other specialists.
Invest Ophthalmol Vis Sci. 2023 Jan 3;64(1):18. doi: 10.1167/iovs.64.1.18.
PURPOSE: Foveoschisis involves the pathologic splitting of retinal layers at the fovea, which may occur congenitally in X-linked retinoschisis (XLRS) or as an acquired complication of myopia. XLRS is attributed to functional loss of the retinal adhesion protein retinoschisin 1 (RS1), but the pathophysiology of myopic foveoschisis is unclear due to the lack of animal models. Here, we characterized a novel nonhuman primate model of myopic foveoschisis through clinical examination and multimodal imaging followed by morphologic, cellular, and transcriptional profiling of retinal tissues and genetic analysis.
METHODS: We identified a rhesus macaque with behavioral and anatomic features of myopic foveoschisis, and monitored disease progression over 14 months by fundus photography, fluorescein angiography, and optical coherence tomography (OCT). After necropsy, we evaluated anatomic and cellular changes by immunohistochemistry and transcriptomic changes using single-nuclei RNA-sequencing (snRNA-seq). Finally, we performed Sanger and whole exome sequencing with focus on the RS1 gene.
RESULTS: Affected eyes demonstrated posterior hyaloid traction and progressive splitting of the outer plexiform layer on OCT. Immunohistochemistry showed increased GFAP expression in Müller glia and loss of ramified Iba-1+ microglia, suggesting macro- and microglial activation with minimal photoreceptor alterations. SnRNA-seq revealed gene expression changes predominantly in cones and retinal ganglion cells involving chromatin modification, suggestive of cellular stress at the fovea. No defects in the RS1 gene or its expression were detected.
CONCLUSIONS: This nonhuman primate model of foveoschisis reveals insights into how acquired myopic traction leads to phenotypically similar morphologic and cellular changes as congenital XLRS without alterations in RS1.
Ophthalmol Retina. 2022 Dec 26:S2468-6530(22)00637-6. doi: 10.1016/j.oret.2022.12.011. Online ahead of print.
We analyzed OCT biomarkers of 65 eyes with treatment-naive RVO and ME. While none of the factors analyzed predicted successful treatment discontinuation, early improvements in vision and DRIL were associated with long-term visual outcomes.
Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay.
Genet Med. 2021 Jan 08;:
Authors: Melo US, Bonner D, Kent Lloyd KC, Moshiri A, Willis B, Lanoue L, Bower L, Leonard BC, Martins DJ, Gomes F, de Souza Leite F, Oliveira D, Kitajima JP, Monteiro FP, Zatz M, Menck CFM, Wheeler MT, Bernstein JA, Dumas K, Spiteri E, Di Donato N, Jahn A, Hashem M, Alsaif HS, Chedrawi A, Alkuraya FS, Kok F, Byers HM
PURPOSE: To identify novel genes associated with intellectual disability (ID) in four unrelated families.
METHODS: Here, through exome sequencing and international collaboration, we report eight individuals from four unrelated families of diverse geographic origin with biallelic loss-of-function variants in UBE4A.
RESULTS: Eight evaluated individuals presented with syndromic intellectual disability and global developmental delay. Other clinical features included hypotonia, short stature, seizures, and behavior disorder. Characteristic features were appreciated in some individuals but not all; in some cases, features became more apparent with age. We demonstrated that UBE4A loss-of-function variants reduced RNA expression and protein levels in clinical samples. Mice generated to mimic patient-specific Ube4a loss-of-function variant exhibited muscular and neurological/behavioral abnormalities, some of which are suggestive of the clinical abnormalities seen in the affected individuals.
CONCLUSION: These data indicate that biallelic loss-of-function variants in UBE4A cause a novel intellectual disability syndrome, suggesting that UBE4A enzyme activity is required for normal development and neurological function.
PMID: 33420346 [PubMed - as supplied by publisher]
Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density.
PLoS Genet. 2020 Dec 28;16(12):e1009190
Authors: Swan AL, Schütt C, Rozman J, Del Mar Muñiz Moreno M, Brandmaier S, Simon M, Leuchtenberger S, Griffiths M, Brommage R, Keskivali-Bond P, Grallert H, Werner T, Teperino R, Becker L, Miller G, Moshiri A, Seavitt JR, Cissell DD, Meehan TF, Acar EF, Lelliott CJ, Flenniken AM, Champy MF, Sorg T, Ayadi A, Braun RE, Cater H, Dickinson ME, Flicek P, Gallegos J, Ghirardello EJ, Heaney JD, Jacquot S, Lally C, Logan JG, Teboul L, Mason J, Spielmann N, McKerlie C, Murray SA, Nutter LMJ, Odfalk KF, Parkinson H, Prochazka J, Reynolds CL, Selloum M, Spoutil F, Svenson KL, Vales TS, Wells SE, White JK, Sedlacek R, Wurst W, Lloyd KKC, Croucher PI, Fuchs H, Williams GR, Bassett D, Gailus-Durner V, Herault Y, Mallon AM, Brown SDM, Mayer-Kuckuk P, Hrabe de Angelis M, IMPC Consortium
The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease.
PMID: 33370286 [PubMed - as supplied by publisher]
Off-label use as a standard of care.
Am J Ophthalmol. 2020 Oct 14;:
Authors: Novack GD, Moshiri A
PMID: 33068530 [PubMed - as supplied by publisher]
Imaging oxygenation of retinal capillaries with depth resolution.
Proc Natl Acad Sci U S A. 2020 Jun 18;:
Authors: Srinivasan VJ, Moshiri A
PMID: 32554605 [PubMed - as supplied by publisher]
Phase I/II randomized study of proton beam with anti-VEGF for exudative age-related macular degeneration: long-term results.
Eye (Lond). 2020 Feb 13;:
Authors: Mukkamala LK, Mishra K, Daftari I, Moshiri A, Park SS
BACKGROUND/OBJECTIVE: To determine if treatment of exudative age-related macular degeneration (eAMD) using proton beam therapy (PBT) combined with intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is safe and effective long term.
SUBJECT/METHODS: Thirty eyes with newly diagnosed eAMD were enrolled in a phase I/II prospective, sham-controlled double-masked university study. Eyes were randomized 1:1:1-24 GyE, 16 GyE or sham radiation, and treated with three initial monthly intravitreal ranibizumab or bevacizumab. Subsequent anti-VEGF reinjection was based on monthly optical coherence tomography and examination for 2 years and standard of care thereafter.
RESULTS: A total of 23 eyes completed 2-year study follow-up, of which 16 maintained monthly follow-up. Mean best-correct visual acuity (BCVA) at 2 years was similar among treatment groups (p > 0.05). The 24 GyE group required fewer anti-VEGF injections when compared with the sham group at 2 years (4.67 ± 1.9 vs 9.67 ± 3.5; p = 0.017). Extended follow-up (mean 4 years) available in 22 eyes showed persistent reduced need for anti-VEGF therapy among eyes treated with 24 GyE compared with sham radiation (2.0 ± 1.6 vs 4.84 ± 2.4 per year, p = 0.008). New and increasing geographic atrophy (GA), noted in some eyes in all treatment groups, resulted in decreased mean BCVA from baseline for the 24 GyE group on extended follow-up (p = 0.009). Possible mild radiation retinopathy noted in 15% of eyes was not visually significant.
CONCLUSIONS: Initial treatment combining PBT (24 GyE) with intravitreal anti-VEGF therapy appears to decrease the need for anti-VEGF reinjection in eyes with newly diagnosed eAMD. Radiation retinopathy risk was low and does not appear visually significant. Long-term vision was limited by GA development especially in the 24 GyE group.
PMID: 32055016 [PubMed - as supplied by publisher]
Identification of Patients with Pentosan Polysulfate Sodium-Associated Maculopathy through Screening of the Electronic Medical Record at an Academic Center.
J Ophthalmol. 2020;2020:8866961
Authors: Higgins K, Welch RJ, Bacorn C, Yiu G, Rothschild J, Park SS, Moshiri A
Aims: This chart review of a quaternary academic medical center electronic medical record (EMR) aimed to identify patients at risk of development of maculopathy with exposure to pentosan polysulfate sodium (PPS).
Methods: A review of electronic medical records of a quaternary medical center of patients with either documented exposure to PPS or diagnosis of interstitial cystitis (IC) from 2007 to 2019 was performed for retinal imaging and visual acuity; the study was conducted in August of 2019.
Results: 216 charts were included for analysis, of which 96 had documented eye exams and 24 had retinal imaging done. We identified three patients with maculopathy in the context of long-term exposure to PPS via chart review, and one additional patient was identified by referral. The median PPS exposure duration was 11 years (range 7 to 19 years). Median logMAR BCVA OD 0.6 range was 0.0-1.9 (approximate Snellen equivalent 20/80 range (20/20-20/1600)) and OS 0.7 range was 0.1-1.9 (approximate Snellen equivalent 20/100 range (20/25-20/1600)). Ultrawidefield color fundus imaging and fundus autofluorescence revealed findings of pigmentary changes and patchy macular atrophy. Optical coherence tomography (OCT) demonstrated outer retinal thinning and increased choroidal transmission coincident with areas of atrophy seen on fundus imaging.
Conclusions: Less than half of patients at risk for development of maculopathy due to exposure to PPS had received eye examinations, suggesting that those at risk are not receiving adequate screening. We found two patients with PPS maculopathy who had relatively preserved central vision, one patient with bitemporal vision loss, and one patient who developed vision loss in both eyes.
PMID: 33489347 [PubMed]
Cytoglobin deficiency potentiates Crb1-mediated retinal degeneration in rd8 mice.
Dev Biol. 2019 Oct 18;:
Authors: Kwon YS, Tham A, Lopez AJ, Edwards S, Woods S, Chen J, Fortunato J, Quiroz A, Javier S, Au I, Clarke M, Humpal D, Lloyd KCK, Thomasy S, Murphy C, Glaser TM, Moshiri A
PURPOSE: The purpose of this study is to determine the effect of Cytoglobin (Cygb) deficiency on Crb1-related retinopathy. The Crb1 cell polarity complex is required for photoreceptor function and survival. Crb1-related retinopathies encompass a broad range of phenotypes which are not completely explained by the variability of Crb1 mutations. Genes thought to modify Crb1 function are therefore important targets of research. The biological function of Cygb involves oxygen delivery, scavenging of reactive oxygen species, and nitric oxide metabolism. However, the relationship of Cygb to diseases involving the Crb1 cell polarity complex is unknown.
METHODS: Cygb knockout mice homozygous for the rd8 mutation (Cygb-/-rd8/rd8) were screened for ocular abnormalities and imaged using optical coherence tomography and fundus photography. Electroretinography was performed, as was histology and immunohistochemistry. Quantitative PCR was used to determine the effect of Cygb deficiency on transcription of Crb1 related cell polarity genes.
RESULTS: Cygb-/-rd8/rd8 mice develop an abnormal retina with severe lamination abnormalities. The retina undergoes progressive degeneration with the ventral retina more severely affected than the dorsal retina. Cygb expression is in neurons of the retinal ganglion cell layer and inner nuclear layer. Immunohistochemical studies suggest that cell death predominates in the photoreceptors. Electroretinography amplitudes show reduced a- and b-waves, consistent with photoreceptor disease. Cygb deficient retinas had only modest transcriptional perturbations of Crb1-related cell polarity genes. Cygb-/- mice without the rd8 mutation did not exhibit obvious retinal abnormalities.
CONCLUSIONS: Cygb is necessary for retinal lamination, maintenance of cell polarity, and photoreceptor survival in rd8 mice. These results are consistent with Cygb as a disease modifying gene in Crb1-related retinopathy. Further studies are necessary to investigate the role of Cygb in the human retina.
PMID: 31634437 [PubMed - as supplied by publisher]
Real-world management and long-term outcomes of diabetic macular oedema with good visual acuity.
Eye (Lond). 2019 Oct 28;:
Authors: Luu KY, Akhter MM, Durbin-Johnson BP, Moshiri A, Tran S, Morse LS, Park SS, Yiu G
PURPOSE: To evaluate the management and long-term outcomes of patients with diabetic macular oedema (DMO) and good initial visual acuity in real-world settings.
METHODS: We reviewed 122 eyes of 100 patients with treatment-naive DMO and initial best-corrected visual acuity (BCVA) of 20/25 or better. We assessed clinical characteristics, logMAR BCVA, central subfield thickness (CST), cumulative intravitreal injections and laser treatments at yearly intervals, and characteristics at time of initial treatment. Linear mixed effects models were used to identify predictors of visual outcomes.
RESULTS: At presentation, mean BCVA was 0.057 ± 0.048 logMAR (Snellen 20/23) and mean CST was 288 ± 57 μm. After a median follow-up of 3 years, 51% of eyes underwent treatment. More eyes underwent intravitreal injection as initial treatment (54%), but lasers were initiated at an earlier time and at better BCVA. Final BCVA was associated with better BCVA (P < 0.001) and earlier timing (P = 0.017) at initial treatment, but not CST at first treatment (P = 0.634) or cumulative number of injections or lasers (P = 0.441-0.606).
CONCLUSION: DMO with good initial visual acuity should be monitored closely, as delay in treatment initiation is associated with worse visual outcomes. BCVA at time of initial treatment is the strongest determinant of final visual acuity.
PMID: 31659287 [PubMed - as supplied by publisher]
Genome-wide screening of mouse knockouts reveals novel genes required for normal integumentary and oculocutaneous structure and function.
Sci Rep. 2019 Aug 01;9(1):11211
Authors: Moore BA, Flenniken AM, Clary D, Moshiri AS, Nutter LMJ, Berberovic Z, Owen C, Newbigging S, Adissu H, Eskandarian M, McKerlie C, International Mouse Phenotyping Consortium, Thomasy SM, Lloyd KCK, Murphy CJ, Moshiri A
Oculocutaneous syndromes are often due to mutations in single genes. In some cases, mouse models for these diseases exist in spontaneously occurring mutations, or in mice resulting from forward mutatagenesis screens. Here we present novel genes that may be causative for oculocutaneous disease in humans, discovered as part of a genome-wide screen of knockout-mice in a targeted single-gene deletion project. The International Mouse Phenotyping Consortium (IMPC) database (data release 10.0) was interrogated for all mouse strains with integument abnormalities, which were then cross-referenced individually to identify knockouts with concomitant ocular abnormalities attributed to the same targeted gene deletion. The search yielded 307 knockout strains from unique genes with integument abnormalities, 226 of which have not been previously associated with oculocutaneous conditions. Of the 307 knockout strains with integument abnormalities, 52 were determined to have ocular changes attributed to the targeted deletion, 35 of which represent novel oculocutaneous genes. Some examples of various integument abnormalities are shown, as well as two examples of knockout strains with oculocutaneous phenotypes. Each of the novel genes provided here are potentially relevant to the pathophysiology of human integumentary, or oculocutaneous conditions, such as albinism, phakomatoses, or other multi-system syndromes. The novel genes reported here may implicate molecular pathways relevant to these human diseases and may contribute to the discovery of novel therapeutic targets.
PMID: 31371754 [PubMed - in process]
Chronic lymphocytic leukaemia presenting as branch retinal artery occlusion and optic disc infiltration.
BMJ Case Rep. 2018 Oct 12;2018:
Authors: Berryman J, Moshiri A, Chang M
PMID: 30317214 [PubMed - in process]
Identification of genetic elements in metabolism by high-throughput mouse phenotyping.
Nat Commun. 2018 Jan 18;9(1):288
Authors: Rozman J, Rathkolb B, Oestereicher MA, Schütt C, Ravindranath AC, Leuchtenberger S, Sharma S, Kistler M, Willershäuser M, Brommage R, Meehan TF, Mason J, Haselimashhadi H, IMPC Consortium, Hough T, Mallon AM, Wells S, Santos L, Lelliott CJ, White JK, Sorg T, Champy MF, Bower LR, Reynolds CL, Flenniken AM, Murray SA, Nutter LMJ, Svenson KL, West D, Tocchini-Valentini GP, Beaudet AL, Bosch F, Braun RB, Dobbie MS, Gao X, Herault Y, Moshiri A, Moore BA, Kent Lloyd KC, McKerlie C, Masuya H, Tanaka N, Flicek P, Parkinson HE, Sedlacek R, Seong JK, Wang CL, Moore M, Brown SD, Tschöp MH, Wurst W, Klingenspor M, Wolf E, Beckers J, Machicao F, Peter A, Staiger H, Häring HU, Grallert H, Campillos M, Maier H, Fuchs H, Gailus-Durner V, Werner T, Hrabe de Angelis M
Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.
PMID: 29348434 [PubMed - in process]
OUTCOMES OF PNEUMATIC RETINOPEXY PERFORMED BY VITREORETINAL FELLOWS.
Retina. 2017 Nov 10;:
Authors: Emami-Naeini P, Vuong VS, Tran S, Morse LS, Moshiri A, Park SS, Yiu G
PURPOSE: To evaluate the anatomical and visual outcomes of patients who underwent pneumatic retinopexy by vitreoretinal fellows.
METHODS: We included 198 eyes (198 patients) that underwent pneumatic retinopexy by vitreoretinal fellows at a single academic institution between November 2002 and June 2016. Main outcomes were single-operation success and final anatomical success in retinal reattachment, as well as visual acuity at 3 months and 6 months after treatment.
RESULTS: Single-operation success rate was 63.6% at 3 months and 59.5% at 6 months. Final anatomical reattachment was achieved in 92.9% (n = 184) and 96.6% (n = 143) at 3 months and 6 months, respectively. Logarithm of the minimum angle of resolution visual acuity improved from 0.72 ± 0.1 (∼20/100 Snellen) at baseline to 0.36 ± 0.06 (∼20/40 Snellen) at 6 months (P < 0.001). There was no statistical difference in anatomical success rates or visual outcomes between cases performed by first- or second-year fellows (P > 0.50). Single-operation success was associated only with size of detachment (P = 0.01). Visual outcome was associated with macula status at baseline (P = 0.032) and number of reoperations (P < 0.001).
CONCLUSION: Anatomical and visual outcomes of fellow-performed pneumatic retinopexy are comparable with those reported in the previous literature.
PMID: 29135800 [PubMed - as supplied by publisher]
Macular Fluid Reduces Reproducibility of Choroidal Thickness Measurements on Enhanced Depth Optical Coherence Tomography.
Am J Ophthalmol. 2017 Oct 14;:
Authors: Wong SS, Vuong VS, Cunefare D, Farsiu S, Moshiri A, Yiu G
PURPOSE: To determine if different types of retinal fluid in the central macula affect the reproducibility of choroidal thickness (CT) measurements on enhanced depth imaging optical coherence tomography (EDI-OCT).
DESIGN: Retrospective reliability analysis.
METHODS: EDI-OCT images were obtained and the choroidal-scleral junction was analyzed through semiautomated segmentation. CT was measured at the fovea and averaged across the central 3-mm horizontal segment. Demographic data, central macular thickness, and type of fluid present were recorded. Intragrader and intergrader repeatability were assessed using the intraclass correlation coefficient (ICC) and coefficient of repeatability (CR).
RESULTS: Of 124 eyes analyzed, 60 (48.4%) had diabetic macular edema, 32 (25.8%) had neovascular age-related macular degeneration, and 32 (25.8%) had other causes of fluid. Intergrader ICC (CR) was 0.95 (74.1 μm) and 0.96 (63.9 μm) for subfoveal and average CT, respectively. CR was similar across various causes of retinal fluid, but was worst for subretinal fluid compared to intraretinal or sub-retinal pigment epithelial fluid. CR also worsened with increasing choroidal thickness, but was not affected by retinal thickness. Intragrader repeatability was generally greater than intergrader values, and followed the same trend.
CONCLUSIONS: The presence of macular fluid reduces CT measurement reproducibility, particularly in eyes with subretinal fluid and greater choroidal thickness. A difference of 74.1 μm in subfoveal CT or 63.9 μm in average CT may be necessary to detect true clinical change in eyes with macular fluid.
PMID: 29038011 [PubMed - as supplied by publisher]
Acute Retinal Necrosis Presenting in Developmentally-delayed Patients with Neonatal Encephalitis: A Case Series and Literature Review.
Ocul Immunol Inflamm. 2017 Aug;25(4):563-568
Authors: Okafor K, Lu J, Thinda S, Schwab I, Morse LS, Park SS, Moshiri A
We report three cases of patients with developmental-delay from neonatal herpetic encephalitis and/or meningitis who presented years later with acute retinal necrosis due to herpes simplex virus. The diagnosis was delayed in all cases due to the patients' inability to verbalize their ocular complaints and cooperate with eye examinations. This case series documents the clinical course, pathophysiologic mechanism, and treatment of acute retinal necrosis in this patient population. Clinicians should understand the importance of prudent consideration of acute retinal necrosis in patients with a history of neonatal herpetic encephalitis and/or meningitis presenting with a red eye.
PMID: 27191471 [PubMed - in process]
Arap1 Deficiency Causes Photoreceptor Degeneration in Mice.
Invest Ophthalmol Vis Sci. 2017 Mar 01;58(3):1709-1718
Authors: Moshiri A, Humpal D, Leonard BC, Imai DM, Tham A, Bower L, Clary D, Glaser TM, Lloyd KC, Murphy CJ
Purpose: Small guanosine triphosphatase (GTPase) ADP-ribosylation factors (Arfs) regulate membrane traffic and actin reorganization under the control of GTPase-activating proteins (GAPs). Arap1 is an Arf-directed GAP that inhibits the trafficking of epidermal growth factor receptor (EGFR) to the early endosome, but the diversity of its functions is incompletely understood. The aim of this study was to determine the role of Arap1 in the mammalian retina.
Methods: Genetically engineered Arap1 knockout mice were screened for ocular abnormalities in the National Institutes of Health Knockout Mouse Production and Phenotyping (KOMP2) Project. Arap1 knockout and wild-type eyes were imaged using optical coherence tomography and fundus photography, and analyzed by immunohistochemistry.
Results: Arap1-/- mice develop a normal appearing retina, but undergo photoreceptor degeneration starting at 4 weeks postnatal age. The fundus appearance of mutants is notable for pigmentary changes, optic nerve pallor, vascular attenuation, and outer retinal thinning, reminiscent of retinitis pigmentosa in humans. Immunohistochemical studies suggest the cell death is predominantly in the outer nuclear layer. Functional evaluation of the retina by electroretinography reveals amplitudes are reduced. Arap1 is detected most notably in Müller glia, and not in photoreceptors, implicating a role for Müller glia in photoreceptor survival.
Conclusions: Arap1 is necessary for normal photoreceptor survival in mice, and may be a novel gene relevant to human retinal degenerative processes, although its mechanism is unknown. Further studies in this mouse model of retinal degeneration will give insights into the cellular functions and signaling pathways in which Arap1 participates.
PMID: 28324111 [PubMed - indexed for MEDLINE]
Senescent Changes and Topography of the Dark-Adapted Multifocal Electroretinogram.
Invest Ophthalmol Vis Sci. 2017 Feb 01;58(2):1323-1329
Authors: Panorgias A, Tillman M, Sutter EE, Moshiri A, Gerth-Kahlert C, Werner JS
Purpose: To investigate the topographic changes of the dark-adapted multifocal electroretinogram (mfERG) across adulthood in the central retina and compare the topography between macular versus extramacular, nasal versus temporal, and inferior versus superior retinal areas.
Methods: Sixty-five subjects (18-88 years) received a comprehensive dilated eye examination to ensure the health of their retina and were tested with a dark-adapted mfERG protocol using a 61-hexagon pattern. The lens absorption of each subject was also estimated using a heterochromatic flicker photometry (HFP) paradigm.
Results: The response amplitude and latency of the dark-adapted mfERG showed a significant change with age, which was best described with a linear model. All the retinal areas examined demonstrated similar aging effects. The extramacular and temporal retina showed higher response amplitude and faster response latency when compared with the macular and nasal retinae, respectively. No difference was found in response amplitude and latency between the inferior and superior retina. The HFP results also showed a significant correlation with age, consistent with senescent increases in short wavelength absorption by the crystalline lens. However, the change in lens absorption did not exceed the magnitude of the change in response amplitude and latency.
Discussion: Our results indicate that there is a decline in dark-adapted retinal activity as measured with the mfERG. These aging processes affect rods and rod-bipolar cells. Their decrease in response can be attributed to both optical and neural factors.
PMID: 28241320 [PubMed - indexed for MEDLINE]
A Review of Innovations in Rhegmatogenous Retinal Detachment Surgical Techniques.
J Ophthalmol. 2017;2017:4310643
Authors: Nemet A, Moshiri A, Yiu G, Loewenstein A, Moisseiev E
Rhegmatogenous retinal detachment (RRD) requires surgical intervention for its repair. There are variable techniques used for this purpose, and they are all being continuously refined. In this review, we detail the recent innovations in surgical management of RRD and proliferative vitreoretinopathy (PVR).
PMID: 28584664 [PubMed]
Endophthalmitis following intravitreal injection of anti-VEGF agents: long-term outcomes and the identification of unusual micro-organisms.
J Ophthalmic Inflamm Infect. 2016 Dec;6(1):2
Authors: Sachdeva MM, Moshiri A, Leder HA, Scott AW
BACKGROUND: While the development of targeted molecular therapy to inhibit vascular endothelial growth factor (VEGF) has revolutionized the treatment and visual prognosis of highly prevalent retinal diseases such as diabetic retinopathy and age-related macular degeneration, each intravitreal injection of these agents carries a small risk of endophthalmitis which can be visually devastating. In the absence of specific guidelines, current management of post-injection endophthalmitis is typically extrapolated from data regarding endophthalmitis occurring after cataract surgery despite potential differences in pathogenic organisms and clinical course. Here, we assess the contribution of intravitreal injections of anti-VEGF agents to all cases of endophthalmitis at our tertiary care referral center and characterize the clinical outcomes and microbial pathogens associated with post-injection endophthalmitis in order to inform management of this serious iatrogenic condition.
RESULTS: During the 7-year study period analyzed, 199 cases of endophthalmitis were identified using billing records. Of these, the most common etiology was post-surgical, accounting for 62 cases (31.2 %), with bleb-associated, endogenous, and corneal ulcer-related infections representing the next most frequent causes, comprising 15.6 % (31/199), 13.1 % (26/199), and 13.6 % (27/199) of all cases, respectively. Intravitreal injections of anti-VEGF agents represented 8.5 % of endophthalmitis (17/199 cases). Intraocular cultures yielded positive results in 75 % of post-injection cases, with the majority associated with coagulase-negative Staphylococcus. Consistent with prior literature, a case of Strep viridans displayed more rapid onset and progression. We also report the first association of Enterobacter cloacae and Lactococcus garvieae with post-injection endophthalmitis. While all but one patient were treated with initial vitreous tap and intravitreal injection of antibiotics, both patients with these rare organisms exhibited persistent vitritis requiring subsequent vitrectomy. Long-term outcomes of post-injection endophthalmitis indicated visual recovery to baseline levels, even with resumption of anti-VEGF agents following resolution of the acute infection.
CONCLUSIONS: Acute endophthalmitis following intravitreal injections of anti-VEGF agents is an uncommon but potentially devastating complication which may be managed effectively with vitreous tap and injection of intravitreal antibiotics. However, persistent vitritis requiring subsequent vitrectomy should raise suspicion for unusual pathogens.
PMID: 26758203 [PubMed]
Repeatability of Choroidal Thickness Measurements on Enhanced Depth Imaging Optical Coherence Tomography Using Different Posterior Boundaries.
Am J Ophthalmol. 2016 Sep;169:104-12
Authors: Vuong VS, Moisseiev E, Cunefare D, Farsiu S, Moshiri A, Yiu G
PURPOSE: To assess the reliability of manual choroidal thickness measurements by comparing different posterior boundary definitions of the choroidal-scleral junction on enhanced depth imaging optical coherence tomography (EDI-OCT).
DESIGN: Reliability analysis.
METHODS: Two graders marked the choroidal-scleral junction with segmentation software using different posterior boundaries: (1) the outer border of the choroidal vessel lumen, (2) the outer border of the choroid stroma, and (3) the inner border of the sclera, to measure the vascular choroidal thickness (VCT), stromal choroidal thickness (SCT), and total choroidal thickness (TCT), respectively. Measurements were taken at 0.5-mm intervals from 1.5 mm nasal to 1.5 mm temporal to the fovea, and averaged continuously across the central 3 mm of the macula. Intraclass correlation coefficient (ICC) and coefficient of reliability (CR) were compared to assess intergrader and intragrader reliability.
RESULTS: Choroidal thickness measurements varied significantly with different posterior boundaries (P < .001 for all). Intergrader ICCs were greater for SCT (0.959-0.980) than for TCT (0.928-0.963) and VCT (0.750-0.869), even in eyes where choroidal-scleral junction visibility was <75%. Intergrader CRs were lower for SCT (41.40-62.31) than for TCT (61.13-74.24) or VCT (72.44-115.11). ICCs and CRs showed greater reliability for averaged VCT, SCT, or TCT measurements than at individual locations. Intragrader ICCs and CRs were comparable to intergrader values.
CONCLUSIONS: Choroidal thickness measurements are more reproducible when measured to the border of the choroid stroma (SCT) than the vascular lumen (VCT) or sclera (TCT).
PMID: 27345731 [PubMed - indexed for MEDLINE]
Association of Baseline Visual Acuity and Retinal Thickness With 1-Year Efficacy of Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema.
JAMA Ophthalmol. 2016 Feb;134(2):127-34
Authors: Wells JA, Glassman AR, Jampol LM, Aiello LP, Antoszyk AN, Baker CW, Bressler NM, Browning DJ, Connor CG, Elman MJ, Ferris FL, Friedman SM, Melia M, Pieramici DJ, Sun JK, Beck RW, Diabetic Retinopathy Clinical Research Network
IMPORTANCE: Comparisons of the relative effect of 3 anti-vascular endothelial growth factor agents to treat diabetic macular edema warrant further assessment.
OBJECTIVE: To provide additional outcomes from a randomized trial evaluating 3 anti-vascular endothelial growth factor agents for diabetic macular edema within subgroups based on baseline visual acuity (VA) and central subfield thickness (CST) as evaluated on optical coherence tomography.
DESIGN, SETTING, AND PARTICIPANTS: Post hoc exploratory analyses were conducted of randomized trial data on 660 adults with diabetic macular edema and decreased VA (Snellen equivalent, approximately 20/32 to 20/320). The original study was conducted between August 22, 2012, and August 28, 2013. Analysis was conducted from January 7 to June 2, 2015.
INTERVENTIONS: Repeated 0.05-mL intravitreous injections of 2.0 mg of aflibercept (224 eyes), 1.25 mg of bevacizumab (218 eyes), or 0.3 mg of ranibizumab (218 eyes) as needed per protocol.
MAIN OUTCOMES AND MEASURES: One-year VA and CST outcomes within prespecified subgroups based on both baseline VA and CST thresholds, defined as worse (20/50 or worse) or better (20/32 to 20/40) VA and thicker (≥400 µm) or thinner (250 to 399 µm) CST.
RESULTS: In the subgroup with worse baseline VA (n = 305), irrespective of baseline CST, aflibercept showed greater improvement than bevacizumab or ranibizumab for several VA outcomes. In the subgroup with better VA and thinner CST at baseline (61-73 eyes across 3 treatment groups), VA outcomes showed little difference between groups; mean change was +7.2, +8.4, and +7.6 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively. However, in the subgroup with better VA and thicker CST at baseline (31-43 eyes), there was a suggestion of worse VA outcomes in the bevacizumab group; mean change from baseline to 1 year was +9.5, +5.4, and +9.5 letters in the aflibercept, bevacizumab, and ranibizumab groups, respectively, and VA letter score was greater than 84 (approximately 20/20) in 21 of 33 (64%), 7 of 31 (23%), and 21 of 43 (49%) eyes, respectively. The adjusted differences and 95% CIs were 39% (17% to 60%) for aflibercept vs bevacizumab, 25% (5% to 46%) for ranibizumab vs bevacizumab, and 13% (-8% to 35%) for aflibercept vs ranibizumab.
CONCLUSIONS AND RELEVANCE: These post hoc secondary findings suggest that for eyes with better initial VA and thicker CST, some VA outcomes may be worse in the bevacizumab group than in the aflibercept and ranibizumab groups. Given the exploratory nature of these analyses and the small sample size within subgroups, caution is suggested when using the data to guide treatment considerations for patients.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01627249.
PMID: 26605836 [PubMed - indexed for MEDLINE]
Ozurdex for the Treatment of a Patient with Birdshot Chorioretinopathy.
Case Rep Ophthalmol. 2015 Sep-Dec;6(3):289-92
Authors: Moisseiev E, Moshiri A
We report a 57-year-old patient with birdshot chorioretinopathy (BCR) who was treated with bilateral Ozurdex injections. The patient's vitritis resolved, and visual acuity improved following this treatment. This is only the second case report focused on the treatment of BCR with Ozurdex and the first to report its use for treating vitritis. A concise review of the literature on the use of intravitreal steroids for this disease is provided. This case serves to report the clinical usefulness of Ozurdex in treating posterior vitritis associated with BCR even in the absence of macular edema.
PMID: 26483669 [PubMed]
Bevacizumab presurgical treatment for proliferative sickle-cell retinopathy-related retinal detachment.
Retin Cases Brief Rep. 2013;7(3):204-5
Authors: Moshiri A, Ha NK, Ko FS, Scott AW
PURPOSE: To report the use of presurgical intravitreal bevacizumab in the context of proliferative sickle-cell retinopathy with retinal detachment.
METHODS: Intravitreal bevacizumab was injected 3 days before the surgical procedure for traction retinal detachment. Vitrectomy, membrane peeling, endolaser, and SF6 gas tamponade were performed. A 37-year-old African American woman presented with hemoglobin sickle-cell disease and temporal retinal detachment with bullous subretinal fluid extending through the fovea associated with an area of active sea-fan retinal neovascularization with preretinal hemorrhage and retinal traction, with 3 associated retinal breaks.
RESULTS: The sea-fan neovascularization associated with the traction retinal detachment and the resultant retinal breaks appeared more fibrotic and les vascular than was noted prior to the pre-operative bevacizumab injection. Segmentation and dissection were performed with minimal bleeding, and retinal traction was relieved without difficulty. This was believed to be atypical in the experience of the surgeons. One month postoperatively, vision measured 20/50, and the retina remained attached.
CONCLUSION: Further study is necessary to clarify the role of anti-vascular endothelial growth factor in the treatment of proliferative sickle cell retinopathy associated retinal detachment.
PMID: 25391106 [PubMed]