Brandon J. Wong

Progression of Hydroxychloroquine Toxic Effects After Drug Therapy Cessation: New Evidence From Multimodal Imaging

IMPORTANCE Given the infrequent occurrence of hydroxychloroquine toxic effects, few data are available about the presenting features and long-term follow-up of patients with hydroxychloroquine retinopathy, making it difficult to surmise the clinical course of patients after cessation of drug treatment. OBJECTIVE To report functional and structural findings of hydroxychloroquine retinal toxic effects after drug therapy discontinuation. DESIGN A retrospective medical record review was performed to identify patients taking hydroxychloroquine who were screened for toxic effects from January 1, 2009, through August 31, 2012, in the eye centers of Northwestern University and the University of Southern California. SETTING Northwestern University Sorrel Rosin Eye Center, Chicago, Illinois, and the Doheny Eye Institute at the University of Southern California, Los Angeles. PARTICIPANTS Seven consecutive patients diagnosed as having hydroxychloroquine retinal toxic effects. MAIN OUTCOME AND MEASURE Retinal toxic effects. RESULTS Seven patients (1 man and 6 women) with a mean age of 55.9 years (age range, 25-74 years) developed retinal toxic effects after using hydroxychloroquine for a mean of 10.4 years (range, 3-19 years). Fundus examination revealed macular pigmentary changes in all 7 patients, corresponding to abnormal fundus autofluorescence (FAF). On spectral domain optical coherence tomography, there was outer retinal foveal resistance (preservation of the external limiting membrane and the photoreceptor layer) in 6 patients. After drug therapy discontinuation, 5 patients experienced outer retinal regeneration (3 subfoveally and 2 parafoveally), with associated functional visual improvement on static perimetry in 2 patients. Over time, FAF remained stable in 3 patients, whereas the remaining patients had a pattern of hypoautofluorescence that replaced areas of initial hyperautofluorescence (2 patients) and enlargement of the total area of abnormal FAF (2 patients). CONCLUSIONS AND RELEVANCE Preservation of the external limiting membrane carries a positive prognostic value in hydroxychloroquine toxic effects because it may be associated with regeneration of the photoreceptor layer and with potential functional visual improvement on static perimetry. The patterns of abnormal FAF persist despite cessation of the medication, with enlargement of the total area of abnormal FAF being the hallmark of severe toxic effects. Relative foveal resistance in hydroxychloroquine toxic effects was supported by this case series. These findings emphasize the importance of early detection and the need for correlating clinical observations with multimodal imaging, particularly FAF and spectral domain optical coherence tomography.

Pilot Study of Doppler Optical Coherence Tomography of Retinal Blood Flow Following Laser Photocoagulation in Poorly Controlled Diabetic Patients

PURPOSE To investigate the effect of panretinal photocoagulation (PRP) on retinal blood flow and shear rate using Doppler Fourier-domain optical coherence tomography (FD-OCT) in poorly controlled diabetics with proliferative diabetic retinopathy (PDR). METHODS This was a prospective interventional pilot study in patients with a new clinical diagnosis of PDR. Retinal blood flow and vessel diameter were measured using Doppler FD-OCT according to a previously described method, immediately before PRP treatment and 7 to 8 weeks after the last PRP session. RESULTS Ten patients with poorly controlled PDR (mean hemoglobin A1C = 9.2 ± 2.0%) and 10 control subjects were included in the study. PDR patients had significantly lower blood flow (∼25%) than control subjects both at baseline (P = 0.01) and after PRP (P = 0.003). Compared to controls, venous and arterial velocities were significantly decreased in diabetics at baseline (∼27%; P < 0.001 and 0.017, respectively) as well as after PRP (P < 0.001 and 0.006, respectively). Compared to controls, venous and arterial shear rates were significantly reduced in diabetics at baseline (∼27%; P = 0.002, 0.03) and after PRP (P = 0.002, 0.03). PRP in this group of PDR patients did not have a statistically significant effect on retinal blood flow or vessel parameters, though there was a trend for decreased arterial diameter (P = 0.09). CONCLUSIONS This is the first study to use Doppler FD-OCT to quantify functional changes in retinal vascular parameters in poorly controlled PDR patients. Compared to controls, blood flow parameters in these patients were decreased at baseline, but did not decrease further following PRP, with important implications related to diabetes control, endothelial function, and therapeutic response.

Multimodal Imaging and Choroidal Volumetric Changes After Half-fluence PDT in Central Serous Chorioretinopathy

Abstract Purpose: The purpose of this study was to identify SD-OCT changes that correspond to leakage on fluorescein (FA) and indocyanine angiography (ICGA) and evaluate effect of half-fluence photodynamic therapy (PDT) on choroidal volume in chronic central serous choroidoretinopathy (CSC). Methods: Retrospective analysis of patients with chronic CSC who had undergone PDT. Baseline FA and ICGA images were overlaid on SD-OCT to identify OCT correlates of FA or ICGA hyperfluorescence. Choroidal volume was evaluated in a subgroup of eyes before and after PDT. Results: Twenty eyes were evaluated at baseline, of which seven eyes had choroidal volume evaluations at baseline and 3 months following PDT. SD-OCT changes corresponding to FA hyperfluorescence were subretinal fluid (73%), RPE microrip (50%), RPE double-layer sign (31%), RPE detachment (15%), and RPE thickening (8%). ICGA hyperfluoresence was correlated in 93% with hyperreflective spots in the superficial choroid. Choroidal volume decreased from 9.35 ± 1.99 to 8.52 ± 1.92 and 8.04 ± 1.7 mm3 (at 1 and 3 months post PDT, respectively, p ≤ 0.001). Conclusions: We identified specific OCT findings that correlate with FA and ICGA leakage sites. SD-OCT is a valuable tool to localize CSC lesions and may be useful to guide PDT treatment. Generalized choroidal volume decrease occurs following PDT and extends beyond PDT treatment site.

A 49-year-old man with unilateral, nontender left eyelid swelling

Brandon J. Wong, BA, Bryan K. Hong, MD, Daman Samrao, MD, Gene H. Kim, MD, and Narsing A. Rao, MD Author affiliations: aKeck School of Medicine, University of Southern California, Los Angeles, California; bDoheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, California; cDepartment of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, California

Acute Lymphoblastic Leukemia Relapse Presenting as Optic Nerve Infiltration.

A girl in her teens with a history of acute lymphoblastic leukemia, diagnosed 7 years before presentation and treated with chemotherapy, presented with 5 days of complete vision loss in the left eye. On examination, visual acuity was 20/20 OD and no light perception OS with a significant afferent pupillary defect. The anterior segment was normal. On fundus examination, the right eye was normal; the left eye showed significant anteriorization, diffuse swelling, and hemorrhage of the optic nerve, 360° of intraretinal hemorrhage, and retinal whitening and edema along the inferior arcade (Figure). Magnetic resonance imaging showed diffuse thickening of the left optic nerve without orbital mass. She was diagnosed with acute lymphoblastic leukemia relapse to the optic nerve causing a secondary retinal vein occlusion and hemiretinal artery occlusion. She was treated emergently with extended beam radiation therapy at 1800 cGy in 10 treatments.

Upregulation of cholesterol 24-hydroxylase following hypoxia–ischemia in neonatal mouse brain

BackgroundMaintenance of cholesterol homeostasis is crucial for brain development. Brain cholesterol relies on de novo synthesis and is cleared primarily by conversion to 24S-hydroxycholesterol (24S-HC) with brain-specific cholesterol 24-hydroxylase (CYP46A1). We aimed to investigate the impact of hypoxia–ischemia (HI) on brain cholesterol metabolism in the neonatal mice.MethodsPostnatal day 9 C57BL/6 pups were subjected to HI using the Vannucci model. CYP46A1 expression was assessed with western blotting and its cellular localization was determined using immunofluorescence staining. The amount of brain cholesterol, 24S-HC in the cortex and in the serum, was measured with enzyme-linked immunosorbent assay (ELISA).ResultsThere was a transient cholesterol loss at 6 h after HI. CYP46A1 was significantly upregulated at 6 and 24 h following HI with a concomitant increase of 24S-HC in the ipsilateral cortex and in the serum. The serum levels of 24S-HC correlated with those in the brain, as well as with necrotic and apoptotic cell death evaluated by the expression of spectrin breakdown products and cleaved caspase-3 at 6 and 24 h after HI.ConclusionEnhanced cholesterol turnover by activation of CYP46A1 represents disrupted brain cholesterol homeostasis early after neonatal HI. 24S-HC might be a novel blood biomarker for severity of hypoxic–ischemic encephalopathy with potential clinical application.