Clinical Outcome of Amniotic Membrane Transplant in Ocular Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis at a Major Burn Unit.

PURPOSE: To analyze the clinical outcome of amniotic membrane transplantation in patients with ocular Stevens-Johnson syndrome/toxic epidermal necrolysis at a major burn unit. DESIGN: Retrospective, non-randomized interventional study. METHODS: A retrospective chart review from April 2014 to January 2022 of 43 patients (85 eyes) at a burn center who underwent amniotic membrane transplantation (AMT) for severe ocular Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), or SJS/TEN was performed. Data regarding the clinical course and outcome were obtained. A comparison between the use of cryopreserved AMT rings (cryoAMT) and dehydrated AMT (deAMT) was also assessed. RESULTS: A total of 85 eyes in 43 patients underwent AMT for severe ocular SJS/TEN. Of the eyes, 72 received deAMT with symblepharon ring, whereas 13 received cryoAMT over the cornea surface. All patients had deAMT placed over the eyelid margins and palpebral conjunctivae and tucked into the fornices. The average best-corrected visual acuity (BCVA) on last follow-up examination was 20/33, 20/30, and 20/34 in all eyes, the cryoAMT group, and the deAMT group, respectively (no significant difference between groups). The most common suspected inciting agent was lamotrigine (17% of all cases). The average long-term complication score was 1.4, with no significant difference between the cryoAMT group (1.6) and the deAMT group (1.4, P = .5). Symblepharon formation was seen more in the cryoAMT group compared to the deAMT group (P < .05). CONCLUSION: The use of AMTs in severe ocular SJS/TEN greatly mitigates long-term complications and improves visual outcome. The retrospective nature of this study limits substantial conclusions regarding any significant difference in outcome between AMT treatment methods. Nevertheless, the use of cryopreserved AMT rings has a similar outcome profile compared to use of dehydrated AMTs with symblepharon ring. Further research is needed to evaluate optimal AMT techniques.

ENDOGENOUS ENDOPHTHALMITIS ASSOCIATED WITH INJECTION DRUG USE COMPARED WITH OTHER ETIOLOGIES.

PURPOSE: To compare features of endogenous endophthalmitis associated with injection drug use (IDU) to endogenous endophthalmitis from other etiologies. METHODS: The authors retrospectively collected data on patients with endogenous endophthalmitis due to IDU or other causes from three academic tertiary care centers over a six-year period. Differences in presenting characteristics, culture results, treatment, and visual acuity were compared between groups. RESULTS: Thirty-eight patients (34%) had IDU-associated endogenous endophthalmitis while 75 patients (67%) had endogenous endophthalmitis from other causes. Compared with patients in the non-IDU group, IDU patients were significantly younger, more frequently male, had longer duration of symptoms at diagnosis, and were less likely to have bilateral disease ( P < 0.05 for all). Injection drug use patients were less likely to have a systemic infection source identified (29% vs. 71%, P < 0.001) or have positive cultures (47% vs. 80%, P < 0.001). The IDU group was less likely to be admitted to the hospital (71% vs. 92%, P = 0.005) and less likely to receive treatment with intravenous antimicrobials (55% vs. 83%, P = 0.003). Visual acuity did not significantly differ between groups. CONCLUSION: Endophthalmitis related to IDU presents in younger patients with less comorbidities and frequently without positive cultures or an identifiable systemic source; therefore, a high index of suspicion is needed to identify this disease.

Barriers in Ophthalmology Residency Applications for Students Identifying as Underrepresented in Medicine: A San Francisco Match Analysis.

OBJECTIVE: There is a significant lack of ophthalmologists who self-identify as underrepresented in medicine (URiM) in the physician workforce. Prior literature has revealed bias in traditional metrics for selection relied on by resident programs such as United States Medical Licensing Examination (USMLE) scores, letters of recommendation (LOR), and induction into medical honors societies such as Alpha Omega Alpha (AOA). The purpose of this study was to elucidate race-based differences in word usage within ophthalmology residency letters of recommendation that may disproportionately affect URiM applicants. DESIGN: This was a retrospective, cohort study. SETTING: This was a multicenter study across the Wilmer Eye Institute at Johns Hopkins, the University of California San Francisco, and the University of North Carolina at Chapel Hill. PARTICIPANTS: San Francisco (SF) Match applications submitted to three ophthalmology residency programs between 2018 and 2020 were reviewed. URiM status, USMLE Step 1 score, and AOA membership were recorded. Letters of recommendation were analyzed using text analysis software. T-tests and chi-squared or Fisher's exact tests were used to compare continuous and categorical variables, respectively. Frequency of word/summary term usage in letters of recommendation were the main outcome measures. RESULTS: Relative to non-URiM applicants, URiM applicants had lower USMLE Step 1 scores (mean difference=7.0; p<0.001). Non-URiM letters of recommendation were more likely to describe applicants as "dependable" (p=0.009) and highlight "research" (p=0.046). URiM letters were more likely to describe applicants as "warm" (p=0.02) and "caring" (p=0.02). CONCLUSIONS: This study identified potential barriers for URiM ophthalmology residency applicants which can help guide future interventions to increase workforce diversity.

Surgical Management of Diabetic Macular Edema.

PURPOSE OF REVIEW: Diabetic macular edema (DME) is the accumulation of fluid in the extracellular space within the macula and is a major cause of visual impairment among patients with diabetes. First-line treatment for DME includes pharmacotherapy with intravitreal anti-vascular endothelial growth factor medications and intravitreal corticosteroids. Alternative therapeutic strategies include laser photocoagulation for non-center involving DME, and surgical options such as pars plana vitrectomy (PPV) with or without internal limiting membrane (ILM) peel in cases with vitreoretinal interface anomalies or DME refractory to pharmacotherapy, and the Port Delivery System (PDS) for sustained release of anti-vascular endothelial growth factor (VEGF) medication. Our aim is to review the existing literature on surgical management of DME including imaging changes in chronic DME and the clinical relevance of surgical intervention. RECENT FINDINGS: Imaging changes associated with DME and a worse prognosis include disorganization of the retinal layer, disruption of both the external limiting membrane (ELM) and ellipsoid zone, and vitreomacular interface abnormalities. Studies involving pars plana vitrectomy with and without ILM peel show anatomic improvement but may not always be associated with significant change in visual outcomes. Early studies lacked detailed imaging of the retinal layers and PPV was likely performed as a last resort. In addition, the novel PDS is surgically implanted into the pars plana and works as a drug reservoir with controlled release of drug. However, it has been recalled in patients with wet age-related macular degeneration due to issues with dislodgement. Surgical interventions for DME include pars plana vitrectomy with and without ILM peel and new surgical therapies for DME such as the PDS and subretinal gene therapy have the potential to reduce the risk of DME progression.

The effect of a brief, unplanned treatment delay on neovascular age-related macular degeneration patients: a retrospective cohort study.

Non-compliance to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy can result in increased disease activity in neovascular age-related macular degeneration (nAMD). Our study aims to determine effects of unplanned delay in anti-VEGF injection treatment for nAMD. This retrospective observational study included patients with delays in receiving intravitreal injections for nAMD treatment from March to May 2020 by at least 21 days. Baseline demographic and clinical characteristics, visual acuity (VA), central macular thickness (CMT) measured on optical coherence tomography (OCT), and duration of delayed treatment were analyzed for 3 time points, the pre-delay visit (v1) and post-delay visits (v2 and v3). Data were compared to age-matched controls treated for nAMD in 2019 without delay. Demographic characteristics were compared using two-sample t-tests for continuous variables and Pearson's chi-square tests for categorical variables. For the two primary outcomes of interest, VA and CMT, means and standard deviations were reported for each combination of group and time. Each outcome was modeled using a linear mixed model with the group, time and group-time interaction as fixed effects. A total of 69 patients (99 eyes) in the treatment delay group and 44 patients (69 eyes) in the control group were identified. Statistically significant differences between control and delayed groups were detected for VA (difference in mean logMAR = 0.16; 95% CI 0.06, 0.27; p = 0.002) and CMT (difference in mean CMT = 29; 95% CI 12, 47; p = 0.001) at v2. No differences were detected for v1 and v3 time points for both outcomes. An unplanned delay in intravitreal injection treatment for nAMD resulted in an increase in CMT and worsening of VA compared to controls observed at v2. At v3, CMT and VA recovered to near v1 levels. This study demonstrates that a one-time, brief interruption in treatment for nAMD results in reversible, temporary worsening.

Melanin-like Nanoparticles as an Alternative to Natural Melanin in Retinal Pigment Epithelium Cells and Their Therapeutic Effects against Age-Related Macular Degeneration.

Melanin is a natural pigment that is widely distributed in many parts of the human body, such as the skin and retinal pigment epithelium (RPE) in eyes. In contrast to skin melanin, which is being constantly synthesized by the epidermal melanocytes, melanin in the RPE does not regenerate. Melanin is known to function as a potential radical scavenger and photoprotective agent. However, the protective effects of melanin against oxidative stress decline with increasing age. This phenomenon has been correlated with the pathogenesis of age-related macular degeneration (AMD). To increase the potential antioxidant and photoprotective characteristics of melanin, we designed a therapeutic strategy for replenishment of melanin using PEGylated synthetic melanin-like nanoparticles (MNPs) in the RPE for the treatment of AMD. We performed experiments using AMD-like cellular and mouse models and demonstrated that MNPs are biocompatible and selectively target reactive oxygen species (ROS) with powerful antioxidant properties. MNPs can traffic and accumulate in the RPE and are exclusively located in cytosol, but not the nucleus and mitochondria of the cells, for at least 3 months after a single-dose intravitreal injection. Our findings demonstrate that MNPs are able to substitute for natural melanin in the RPE and suggest the potential efficacy of MNPs as a natural radical scavenger against oxidative stress in ROS-related diseases, such as AMD.

Systemic and Ocular Adverse Events with Intravitreal Anti-VEGF Therapy Used in the Treatment of Diabetic Retinopathy: a Review.

PURPOSE OF REVIEW: Intravitreal anti-vascular endothelial growth factor (VEGF) agents are used routinely in the management of neovascular conditions including proliferative diabetic retinopathy and diabetic macular edema. While the efficacy of anti-VEGF agents has been well-validated, their ocular and systemic adverse events should always be considered and discussed with patients. The aim of this review is to discuss the most recent literature reports regarding the various ocular and systemic adverse events associated with intravitreal anti-VEGF treatment in diabetic retinopathy. RECENT FINDINGS: The most frequently reported adverse ocular events include subconjunctival hemorrhage, vitreous hemorrhage, increased intraocular pressure, uveitis, endophthalmitis, ocular surface disease, and traumatic cataract. Subconjunctival hemorrhage and vitreous hemorrhage are the most common ocular adverse events reported with intravitreal anti-VEGF treatment. The most serious (though rare) ocular adverse events include endophthalmitis and rhegmatogenous retinal detachment. A consensus regarding the association of systemic adverse events (such as myocardial infarction, stroke, and death) with intravitreal anti-VEGF treatments has not been established. Intravitreal anti-VEGF therapy is used in the treatment of diabetic retinopathy, macular degeneration, and other diseases. These agents are associated with a variety of ocular and systemic adverse events that ophthalmologists should always consider.

A Pilot Study Assessing Treatment Outcomes in Neovascular Glaucoma Using Ahmed Glaucoma Valve with and without Cyclophotocoagulation.

Purpose: The purpose of this retrospective pilot study was to examine the short-term effect of simultaneous Ahmed Glaucoma Valve implantation and cyclophotocoagulation on postoperative outcomes in patients with neovascular glaucoma. Methods and materials: Patient charts were selected for inclusion in this study if they carried a diagnosis of neovascular glaucoma and underwent Ahmed glaucoma valve implantation only, Ahmed glaucoma valve implantation with cyclophotocoagulation, or cyclophotocoagulation only. A total of 55 eyes of 54 patients were selected for data collection and analysis. Main outcome measures included 1-, 3-, and 6-month intraocular pressure and occurrence of the hypertensive phase. Other outcomes included visual acuity, surgical complication rate, and a number of 6-month postoperative ophthalmic medications. Results: A significantly lower intraocular pressure was seen in the group that received Ahmed glaucoma valve implantation + cyclophotocoagulation compared to the Ahmed glaucoma valve-only group at 3 and 6 months (p = 0.03 and <0.001, respectively). The difference in the occurrence of the hypertensive phase between the Ahmed glaucoma valve-only group and the Ahmed glaucoma valve + cyclophotocoagulation group approached but did not reach significance (p = 0.052). A significantly lower intraocular pressure was also seen in the cyclophotocoagulation-only group compared to the Ahmed glaucoma valve-only group at 3 months (p = 0.006). Conclusion: Simultaneous Ahmed glaucoma valve implantation and cyclophotocoagulation significantly lowered intraocular pressure at 3 and 6 months compared to Ahmed glaucoma valve implantation alone in patients with neovascular glaucoma. Clinical significance: Neovascular glaucoma is difficult to manage medically and surgically. When surgery is performed, intraocular pressure often remains elevated postoperatively despite aggressive medical management. This study examines a novel method to lower intraocular pressure after Ahmed glaucoma valve implantation in patients with neovascular glaucoma. How to cite this article: Ford RL, Knight ORJ, Klifto MR, et al. A Pilot Study Assessing Treatment Outcomes in Neovascular Glaucoma Using Ahmed Glaucoma Valve with and without Cyclophotocoagulation. J Curr Glaucoma Pract 2022;16(1):4-10.

Role of Optical Coherence Tomography Angiography Imaging in Patients with Diabetes.

PURPOSE OF REVIEW: Ocular manifestations in patients with diabetes mellitus (DM) can present as microvascular changes. These microvascular changes can be challenging to identify on exams, and imaging technologies have commonly aided in the diagnosis and management of patients with DM. Optical coherence tomography angiography (OCTA) provides noninvasive image segmentation of various layers of the retina and choroid. Also, post-processing of images and associated quantitative measurements offer potential clinical enhancements. Our aim is to review the current evidence on the utility of OCTA for patients with DM. RECENT FINDINGS: Research suggests OCTA to potentially provide potential clinical enhancements and alternative methods in detecting subclinical manifestation of diabetic retinopathy, staging diabetic retinopathy, management of diabetic macular edema, and monitoring of systemic markers in patients with diabetes mellitus. OCTA is a promising but relatively new modality, and differences in terminology, research designs, and image processing techniques provide a difficult landscape to navigate. Standardization within further validation is needed to determine the extent of OCTA's clinical utility, but the current literature suggests the potential for earlier detection of ocular manifestations in patients with DM, additional objective measurements for grading and management, and opportunity for additional biomarkers for treatment outcomes.

Hyperviscosity Retinopathy Due to Waldenström Macroglobulinemia: A Case Report and Literature Review.

Purpose: This case report describes a case of hyperviscosity retinopathy secondary to the rare systemic hematologic malignant neoplasm Waldenström macroglobulinemia. Methods: Fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography were used as imaging modalities to characterize this pathology. Results: A 51-year-old man presented with hyperviscosity retinopathy and uniquely angiographically silent serous macular detachment. Over a 6-month period, he was treated with systemic and local therapies with little improvement in the hyperviscosity retinopathy, serous macular detachments, or visual acuity. Conclusions: Hyperviscosity retinopathy secondary to Waldenström macroglobulinemia presents a challenge to treating ophthalmologists given its rarity and the range of treatment responses described in the literature. Our patient's lack of response to antivascular endothelial growth factor and normal findings in OCT angiography and fluorescein angiography suggested the mechanism of subretinal fluid accumulation was not vascular endothelial growth factor mediated. Visual prognosis was guarded.

Bordetella Holmesii: An Unusual Cause of Endogenous Endophthalmitis in a Patient With Sickle Cell Disease.

Purpose: This case report describes a rare organism causing endogenous endophthalmitis in a patient with sickle cell disease. Methods: A case report was conducted. Results: A 41-year-old man with sickle cell disease presented with acute onset of blurry vision of the right eye. His visual acuity was counting fingers in the right eye and 20/20 in the left eye. He had ophthalmic findings of hypopyon and vitritis in the right eye, consistent with endophthalmitis. He was treated with intravitreal and systemic antibiotics. Vitreous cultures grew Bordetella holmesii. His visual acuity at follow-up visits improved to 20/40 in the setting of improved vitritis. Conclusions: This is the first case describing B holmesii, a rare causative organism of endogenous endophthalmitis, in a patient with sickle cell disease. More studies are needed to improve the early detection and treatment of this unusual organism.

Anxiety and Depression in Patients With Retinitis Pigmentosa.

Purpose: Retinitis pigmentosa (RP) is a chronic progressive disease with no curative treatments. Understanding the variables involved with improving patients' quality of life is important in managing this population. The literature investigating the relationship of anxiety and depression with RP relies on the analysis of smaller subset populations of patients with RP, and no study has quantified the effect size of the potential association. This study aims to elucidate and quantify the association between RP, anxiety, and depression. Methods: A retrospective case-control study was conducted of 6 093 833 medical records within the University of North Carolina Hospital and outpatient clinic system from July 1, 2004, to August 30, 2019. Patients with a diagnosis of RP, anxiety, and depression were identified within the Carolina Data Warehouse for Health by International Classification of Diseases, Ninth and Tenth Revision codes. Results: From the base population of 6 093 833 patients' medical records, 690 patients were diagnosed with RP, 253 065 with anxiety, and 232 541 with depression. Patients with RP have an odds ratio, adjusted for sex and age, of 4.915 (95% CI, 4.035-5.987) for having comorbid anxiety, 5.609 (95% CI, 4.622-6.807) for comorbid depression, and 4.130 (95% CI, 3.187-5.353) for comorbid anxiety and depression. Conclusions: Patients with RP have a higher prevalence of anxiety and depression, with increased odds of approximately 5 to 6 times for also carrying a diagnosis of anxiety or depression and about 4 times for carrying diagnoses of anxiety and depression compared with the general population.

Ophthalmic manifestations of coronavirus disease 2019 and ocular side effects of investigational pharmacologic agents.

PURPOSE OF REVIEW: To compile and report the ocular manifestations of coronavirus disease 2019 (COVID-19) infection and summarize the ocular side effects of investigational treatments of this disease. RECENT FINDINGS: Conjunctivitis is by far the most common ocular manifestation of COVID-19 with viral particles being isolated from tears/secretions of infected individuals. Multiple therapeutic options are being explored across a variety of medication classes with diverse ocular side effects. SUMMARY: Eye care professionals must exercise caution, as conjunctivitis may be the presenting or sole finding of an active COVID-19 infection. While no currently studied therapeutic agents have been found to reliably treat COVID-19, early vaccination trials are progressing and show promise. A video abstract is available for a more detailed summary. VIDEO ABSTRACT: http://links.lww.com/COOP/A36.

A Case of Choroidal and Vitreous Hemorrhage Following Micropulse Transscleral Cyclophotocoagulation.

Choroidal hemorrhages involve bleeding into the potential space between the choroid and sclera and are a serious ocular complication. Common causes of choroidal hemorrhages include intraocular surgeries, such as scleral buckling, cataract extractions, and glaucoma filtering procedures, or trauma. We report a case of choroidal and vitreous hemorrhage after micropulse cyclophotocoagulation. An 82-year-old female presented postoperative day 1 with blurry vision and pain in her right eye. Examination showed that she had a choroidal hemorrhage, 200 degrees of ciliary body swelling, and vitreous hemorrhage. Although the choroidal hemorrhage resolved with steroids, the vitreous hemorrhage required pars plana vitrectomy. To the best of our knowledge, this article discusses the first reported case of choroidal and vitreous hemorrhage due to micropulse cyclophotocoagulation.

A cerium oxide loaded glycol chitosan nano-system for the treatment of dry eye disease.

Dry eye (DE) disease is an uprising health epidemic that directly affects the surface of the eye. We developed a water soluble cerium oxide loaded glycol chitosan nanoparticle as a new type of eye drop, namely GCCNP (glycol chitosan cerium oxide nanoparticles). GCCNP is capable of scavenging cellular reactive oxygen species (ROS) for the treatment of DE disease. The antioxidative effects of GCCNP were assessed in mice primary corneal and conjunctival cells in vitro and in a DE murine model in vivo. GCCNP's effect on the DE models was assessed via histological evaluations, migration assays, cell viability assays, cellular uptake analyses, intracellular ROS scavenging assays, wound healing assays, mitochondrial membrane potential readings, corneal fluorescein staining, tear volume concentrations, tear film break up time analyses, and lastly, analytical/spectroscopic analyses of GCCNP eye drop formulations. Spectroscopic analysis showed that cerium oxide was entrapped into the glycol chitosan (GC). The solubility of cerium in GC (GCCNP) increased to 709.854±24.3µg/ml compared to its original solubility in cerium oxide, which was measured as 0.020±0.002µg/ml. GCCNP had no cytotoxic effect and showed improvements on dry eye disease models by stabilizing the tear film, scavenging ROS, up-regulating SOD, promoting and maintaining corneal and conjunctival cell growth and integrity. We provided convincing evidence that GCCNP is an effective treatment for DE and may represent a potential new class of drug for DE disease.

Evolution of Choroidal Neovascularization due to Presumed Ocular Histoplasmosis Syndrome on Multimodal Imaging including Optical Coherence Tomography Angiography.

A 37-year-old Caucasian woman presented with acute decrease in central vision in her right eye and was found to have subfoveal choroidal neovascularization (CNV) due to presumed ocular histoplasmosis syndrome (POHS). Her visual acuity improved from 20/70 to 20/20 at her 6-month follow-up, after 3 consecutive monthly intravitreal bevacizumab injections were initiated at her first visit. Although no CNV activity was seen on fluorescein angiography (FA) or spectral-domain optical coherence tomography (SD-OCT) at her 2-month, 4-month, and 6-month follow-up visits, persistent flow in the CNV lesion was detected on optical coherence tomography angiography (OCTA). OCTA shows persistent vascular flow as well as changes in vascular flow in CNV lesions associated with POHS, indicating the continued presence of patent vessels and changes in these CNV lesions, even when traditional imaging of the lesion with OCT and FA indicates stability of the lesion with no disease activity. Additional cases with longitudinal follow-up are needed to assess how OCTA should be incorporated into clinical practice.

Correlation of Ultra-Widefield Fluorescein Angiography and OCT Angiography in Sickle Cell Retinopathy.

PURPOSE: To determine whether the degree of peripheral nonperfusion seen on ultra-widefield (UWF) fluorescein angiography (FA) correlates with measures of macular vascular flow as seen on OCT angiography (OCTA) in sickle cell retinopathy. DESIGN: Prospective, observational study. PARTICIPANTS: Patients with sickle cell disease undergoing an eye examination at an urban, tertiary medical center. METHODS: All patients underwent dilated fundus examination as well as UWF FA and macular OCTA imaging on the same day. The peripheral nonperfusion seen on UWF FA was measured to calculate an ischemic index (visualized nonperfusion/total visualized retinal area × 100%), and OCTA measurements of macular vessel density were recorded. The degree of peripheral nonperfusion and vessel density were then correlated. MAIN OUTCOME MEASURES: Correlation between ischemic index as seen on UWF FA and macular vessel density on OCTA. RESULTS: Thirty-six eyes from 19 patients (10 women, 9 men) with a mean age of 30.8 years were included. Sickle genotypes included 14 patients with SS (73.7%), 4 with SC (21.1%), and 1 with ß-thalassemia (5.2%). Average ischemic index was 4.4% for all eyes and was found to be higher in patients with sickle SC (8.0%) than in those with sickle SS (3.2%; P = 0.01). Ischemic index also was higher in those with proliferative sickle cell retinopathy (9.3%) than in those without (2.8%; P < 0.01). Ischemic index on UWF FA showed a statistically significant correlation (P < 0.05) with vessel density on OCTA in the temporal subfield of the superficial capillary plexus and in all subfields of the deep capillary plexus. CONCLUSIONS: Peripheral nonperfusion seen on UWF FA is greater in those with sickle SC disease and proliferative retinopathy and is correlated with macular vessel density on OCTA, especially the deep retinal plexus.

Choroideremia Is a Systemic Disease With Lymphocyte Crystals and Plasma Lipid and RBC Membrane Abnormalities.

PURPOSE: Photoreceptor neuronal degenerations are common, incurable causes of human blindness affecting 1 in 2000 patients worldwide. Only half of all patients are associated with known mutations in over 250 disease genes, prompting our research program to identify the remaining new genes. Most retinal degenerations are restricted to the retina, but photoreceptor degenerations can also be found in a wide variety of systemic diseases. We identified an X-linked family from Sri Lanka with a severe choroidal degeneration and postulated a new disease entity. Because of phenotypic overlaps with Bietti's crystalline dystrophy, which was recently found to have systemic features, we hypothesized that a systemic disease may be present in this new disease as well. METHODS: For phenotyping, we performed detailed eye exams with in vivo retinal imaging by optical coherence tomography. For genotyping, we performed whole exome sequencing, followed by Sanger sequencing confirmations and cosegregation. Systemic investigations included electron microscopy studies of peripheral blood cells in patients and in normal controls and detailed fatty acid profiles (both plasma and red blood cell [RBC] membranes). Fatty acid levels were compared to normal controls, and only values two standard deviations above or below normal controls were further evaluated. RESULTS: The family segregated a REP1 mutation, suggesting choroideremia (CHM). We then found crystals in peripheral blood lymphocytes and discovered significant plasma fatty acid abnormalities and RBC membrane abnormalities (i.e., elevated plasmalogens). To replicate our discoveries, we expanded the cohort to nine CHM patients, genotyped them for REP1 mutations, and found the same abnormalities (crystals and fatty acid abnormalities) in all patients. CONCLUSIONS: Previously, CHM was thought to be restricted to the retina. We show, to our knowledge for the first time, that CHM is a systemic condition with prominent crystals in lymphocytes and significant fatty acid abnormalities.