Members > Ala Moshiri, M.D., Ph.D.
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.
Chronic lymphocytic leukaemia presenting as branch retinal artery occlusion and optic disc infiltration.
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.
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.
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).
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.
Acute Retinal Necrosis Presenting in Developmentally-delayed Patients with Neonatal Encephalitis: A Case Series and Literature Review.
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.
Venous Neovascularization in a Recipient of a Pediatric Kidney Transplant.
Arap1 Deficiency Causes Photoreceptor Degeneration in Mice.
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.
Senescent Changes and Topography of the Dark-Adapted Multifocal Electroretinogram.
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.
The Management of Retinal Detachment: Techniques and Perspectives.
A Review of Innovations in Rhegmatogenous Retinal Detachment Surgical Techniques.
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).
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.
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).
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).
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.
Ozurdex for the Treatment of a Patient with Birdshot Chorioretinopathy.
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.
Morphogenetic model for radial streaking in the fundus of the carrier state of X-linked albinism.
Bevacizumab presurgical treatment for proliferative sickle-cell retinopathy-related retinal detachment.
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.
Understanding and reporting visual acuity measurements in publications of clinical research.