Topography-guided excimer laser ablation.

PURPOSE OF REVIEW: Currently, the most commonly performed corneal refractive surgery is laser-assisted in-situ keratomileusis (LASIK). Customized forms of LASIK have been developed, which have allowed for improved outcomes and the enhanced correction of higher order aberrations (HOAs). This review discusses one form of custom LASIK, topography-guided LASIK, including factors involved in preoperative planning, and advantages and disadvantages compared with other forms of keratorefractive surgery. RECENT FINDINGS: Various treatment-planning approaches addressing discrepancies between the refractive and topographic astigmatic magnitude and axis have been used successfully, although there is debate regarding a superior method in the literature. SUMMARY: There are many forms of custom LASIK, which provide excellent outcomes. Topography-guided LASIK may be of particular use in highly aberrated corneas and may also provide outstanding outcomes in healthy eyes given its emphasis on treating the primary refractive surface of the eye.

Infectious Crystalline Keratopathy Secondary to Mycobacterium chelonae.

PURPOSE: The aim of this study was to describe the clinical presentation and multimodal imaging of a patient diagnosed with infectious crystalline keratitis (ICK) secondary to Mycobacterium chelonae . METHODS: This is a case report of a patient with a crystalline corneal infiltrate imaged with anterior segment optical coherence tomography and in vivo scanning laser confocal microscopy. Bacterial, fungal, acanthamoeba, and acid-fast cultures were performed to identify the causal pathogen. RESULTS: Examination revealed a white stellate opacity in the midstroma underlying the scalloped border of an area of central corneal stromal thinning, consistent with a diagnosis of ICK. Anterior segment optical coherence tomography demonstrated a hyperreflective diamond-shaped opacity located at a depth of 334 µm, which demonstrated multiple stellate projections on in vivo scanning laser confocal microscopy. The acid-fast culture was positive for Mycobacterium chelonae . CONCLUSIONS: Although ICK is most commonly associated with Streptococcus species, it may be secondary to atypical bacteria including Mycobacterium species, underscoring the importance of diagnostic imaging and collecting corneal cultures to identify the pathogenic organism.

Presumed retinal pericapillary astrocytic hamartoma: multimodal imaging findings of a novel hamartomatous lesion.

PURPOSE: To describe the multimodal imaging findings of retinal lesions that clinically resemble retinal astrocytic hamartomas (RAHs), but also have unique characteristics that we believe represent a novel variant. METHODS: Observational study. Five eyes in five patients with solitary retinal lesion evaluated at the retina division of three institutions. We describe the multimodal imaging findings including fundus photography, fundus autofluorescence, fluorescein angiography, spectral-domain optical coherence tomography (OCT), swept-source OCT, swept-source OCT angiography and ultrasonography. RESULTS: The retinal lesions described shared similar appearance to RAHs but demonstrated unique features such as glistening granular appearance on fundus photographs with perivascular hyperreflectivity with OCT and OCT angiography. CONCLUSION: The lesions described herein appear to have unique characteristics that warrant a designation as a novel RAH variant. The name presumed retinal pericapillary astrocytic hamartoma is suggested.

Comparison of rotational stability and repositioning rates of 2 presbyopia-correcting and 2 monofocal toric intraocular lenses.

PURPOSE: To compare the rotational stability of 2 commonly used toric presbyopia-correcting (PC) intraocular lenses (IOLs) and their monofocal toric counterparts. SETTING: Single 2-surgeon private practice. DESIGN: Retrospective study. METHODS: This study included 2 cohorts: (1) all eyes receiving a toric ReSTOR (n = 61 eyes, 49 patients) or toric Symfony (n = 779 eyes, 520 patients) IOL from September 2016 to January 2019; and (2) all eyes receiving an AcrySof (n = 2 393) or TECNIS (n = 731) monofocal toric IOL (TIOL) from April 2015 to January 2019. Eyes were only excluded if digital marking could not be used. All patients had image-guided digital marking to verify TIOL position at the conclusion of surgery. Postoperative rotation was determined by dilated examination performed later on the day of surgery or the following morning. RESULTS: The toric ReSTOR IOL was more likely to rotate 5 degrees or less than the toric Symfony IOL, 91.8% vs 79.0% (P = .01). This remained true for rotation of 10 degrees or less (100% vs 89.5%, P < 0.003). The mean rotation was 2.3 degrees for toric ReSTOR IOL compared with 4.5 for toric Symfony IOL (P = .01). Statistically significantly more eyes with toric Symfony IOL required a return to the operating room for repositioning (6.9% vs 0%, P < .03). More TECNIS monofocal TIOL eyes required surgical repositioning than AcrySof monofocal TIOL eyes (3.5% vs 1.2%, P < .001). CONCLUSIONS: Between these PC-TIOLs, the Symfony IOL was more likely to rotate and to require surgical repositioning than the ReSTOR IOL. The TECNIS TIOL built on the same platform as the Symfony IOL was more likely to require surgical repositioning than that by the AcrySof TIOL. Despite comparable rotational stability between the Symfony and TECNIS monofocal TIOLs, the Symfony was twice as likely to require surgical repositioning.

Optic nerve head reactive retinal astrocytic tumor treated with photodynamic therapy.

PURPOSE: To describe the unusual presentation and the treatment course of a case of bilateral optic nerve head reactive retinal astrocytic tumor (RRAT). OBSERVATIONS: A 29 year-old woman with bilateral optic disc masses presented with declining vision refractory to anti-vascular endothelial growth factor (VEGF) injections. After total loss of vision in her left eye, diagnostic enucleation and histopathology was consistent with RRAT. Staged photodynamic therapy (PDT) treatments over a period of four months in the better seeing eye resulted in stabilization of vision, improvement in intraretinal and subretinal fluid, and shrinkage of the optic disc mass. CONCLUSIONS: In this unusual case of bilateral vision-threatening optic nerve head RRAT that were refractory to multiple therapies including anti-VEGF injections, PDT demonstrated safety and efficacy. Diagnostic work-up included whole exome sequencing (WES) that was negative for mutations in genes related to von-Hippel-Lindau (VHL), neurofibromatosis, tuberous sclerosis, and hypoxia-inducible factor (HIF)-2 α .

Parafoveal vessel changes in primary open-angle glaucoma and normal-tension glaucoma using optical coherence tomography angiography.

PURPOSE: To evaluate parafoveal and peripapillary perfusion in healthy, glaucoma suspect, normal-tension glaucoma, and primary open-angle glaucoma subjects. PATIENTS AND METHODS: This was a retrospective cross-sectional study with optical coherence tomography angiography imaging with RTVue XR Avanti (Optovue, Inc., Fremont, CA) of 56 eyes (14 healthy, 14 glaucoma suspect, 16 normal-tension glaucoma, and 12 primary open-angle glaucoma) at a tertiary academic referral center. Parafoveal and peripapillary superficial vessel density and parafoveal superficial retinal thickness were the main parameters of interest. Area under receiver operating characteristic curves were calculated. RESULTS: There were significant decreases in parafoveal superficial vessel density in primary open-angle (40.06±4.54%, P<0.001) and normal-tension glaucoma (42.82±5.16%, P=0.010) but not suspect eyes (45.72±4.37%, P=0.916) compared to healthy eyes (48.10±2.82%). Similarly, decreases were observed in parafoveal inner retinal thickness in primary open-angle (83.19±14.29 µm, P<0.001) and normal-tension glaucoma eyes (94.97±12.44 µm, P=0.035), but not suspect eyes (99.93±9.00 µm, P=0.648), compared to healthy controls (107.00±9.55 µm). Only primary open-angle glaucoma eyes displayed significant changes in peripapillary vessel density (37.63±7.19%) compared to healthy controls (49.12±2.80%, P<0.001). Further statistical adjustment for sex and age revealed a significant decrease in parafoveal vessel density in suspects relative to controls (P=0.039). Diagnostic accuracy of parafoveal vessel density was high with an area under the curve of 0.833±0.073 for normal-tension glaucoma and 0.946±0.049 for primary open-angle glaucoma. CONCLUSION: Parafoveal vessel density was significantly reduced in glaucomatous eyes, with good diagnostic accuracy. These findings provide further evidence that these changes may be useful in the diagnosis and monitoring of disease in glaucoma patients.

Characterization of Inner Retinal Hyperreflective Alterations in Early Cognitive Impairment on Adaptive Optics Scanning Laser Ophthalmoscopy.

Purpose: To examine inner retinal hyperreflective features on adaptive optics scanning laser ophthalmoscopy (AOSLO) in individuals with early cognitive impairment. Methods: In this prospective, cross-sectional study, we enrolled 12 participants with either amnestic mild cognitive impairment (aMCI, n = 10) or early dementia due to Alzheimer's disease (eAD, n = 2) and 12 age-, sex-, and race-matched cognitively normal controls. All participants completed AOSLO imaging of the inner retina. AOSLO montages of the peripapillary area were graded for hyperreflective features including granular membranes, mottled membranes, and nummular features. Regions of interest on AOSLO were compared qualitatively to corresponding optical coherence tomography (OCT) cross sections. OCT was also used to analyze peripapillary retinal nerve fiber layer (RNFL) thickness. Results: Cognitively impaired individuals had a significantly higher number of granular membranes with a larger overall area compared to controls. The proportion of cognitively impaired individuals with two or more granular membranes was 41.7% compared to none in the control group. Granular membrane area was also inversely correlated with cognitive performance on the Montreal Cognitive Assessment. There was no difference between the two groups in terms of other membrane types or RNFL thickness. Conclusions: Individuals with early cognitive impairment related to Alzheimer's show hyperreflective granular membranes on high-resolution imaging, which we hypothesize to be manifestations of inner retinal gliosis. The presence of these subtle hyperreflective membranes may obscure underlying RNFL thinning in these eyes on OCT imaging. The distinctive phenotype of granular membranes surrounding the optic nerve on AOSLO may represent a new potential biomarker of early Alzheimer's.

An overview of optical coherence tomography angiography and the posterior pole.

Optical coherence tomography angiography is a relatively new, noninvasive technology that has revolutionized imaging of the retinal and choroidal microvasculature. This technology is based on the detection of movement or changes that represent moving red cells in sequential optical coherence tomography scans. As with other established imaging technologies, it has unique benefits as well as certain disadvantages, which include a limited field of view and vulnerability to imaging artifacts. However, software and hardware improvements are continually evolving to mitigate these limitations. Optical coherence tomography angiography has been used to gain a better understanding of microvascular changes across a spectrum of ocular diseases including diabetic retinopathy, age-related macular degeneration, glaucoma, and retinal vein occlusions. In this article, we review algorithms and techniques commonly utilized in optical coherence tomography angiography systems and compare optical coherence tomography angiography to fluorescein angiography, the current gold standard for imaging the retinal vasculature. In addition, we provide an overview of important optical coherence tomography angiography findings in a variety of ocular diseases. Although the clinical role of this technology is still poorly defined, optical coherence tomography angiography has the potential to become an invaluable tool in the diagnosis and monitoring of vascular pathologies.

CHARACTERIZATION AND CORRELATION OF "JAMPOL DOTS" ON ADAPTIVE OPTICS WITH FOVEAL GRANULARITY ON CONVENTIONAL FUNDUS IMAGING.

PURPOSE: To describe features characteristic of multiple evanescent white dot syndrome (MEWDS) using adaptive optics scanning laser ophthalmoscopy (AOSLO). METHODS: Six women (seven eyes) who presented with MEWDS between June 2014 and April 2017 underwent ophthalmologic examinations and multimodal imaging including infrared, AOSLO, and spectral domain optical coherence tomography. RESULTS: Bright hyperreflective lesions on AOSLO throughout the course of MEWDS could be correlated to the hyperreflective dots of foveal granularity on infrared imaging without apparent corresponding changes on spectral domain optical coherence tomography. During the acute phase of MEWDS, extrafoveal hyperreflective dots were also visible on AOSLO and infrared and were associated with accumulations of hyperreflective material above the retinal pigment epithelium on spectral domain optical coherence tomography. CONCLUSION: Foveal granularity on conventional fundus imaging could be correlated with hyperreflective lesions visible on AOSLO. We hypothesize that these hyperreflective lesions, "Jampol dots," are the foveal corollaries of the same process associated with the classic "dot" lesions in MEWDS. Based on the intact photoreceptor mosaic on AOSLO, we surmise that this material is accumulating at the level of the retinal pigment epithelium.

MULTILEVEL ISCHEMIA IN DISORGANIZATION OF THE RETINAL INNER LAYERS ON PROJECTION-RESOLVED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To examine the relationship between ischemia and disorganization of the retinal inner layers (DRIL). METHODS: Cross-sectional retrospective study of 20 patients (22 eyes) with diabetic retinopathy presenting to a tertiary academic referral center, who had DRIL on structural optical coherence tomography (OCT) using Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany) and OCT angiography with XR Avanti (Optovue Inc, Fremont, CA) on the same day. Optical coherence tomography angiography images were further processed to remove flow signal projection artifacts using a software algorithm adapted from recent studies. Retinal capillary perfusion in the superficial capillary plexuses, middle capillary plexuses, and deep capillary plexuses, as well as integrity of the photoreceptor lines on OCT was compared in areas with DRIL to control areas without DRIL in the same eye. RESULTS: Qualitative assessment of projection-resolved OCT angiography of eyes with DRIL on structural OCT demonstrated significant perfusion deficits compared with adjacent control areas (P < 0.001). Most lesions (85.7%) showed superimposed superficial capillary plexus and/or middle capillary plexus nonperfusion in addition to deep capillary plexus nonflow. Areas of DRIL were significantly associated with photoreceptor disruption (P = 0.035) compared with adjacent DRIL-free areas. CONCLUSION: We found that DRIL is associated with multilevel retinal capillary nonperfusion, suggesting an important role for ischemia in this OCT phenotype.

Essential function of NHE8 in mouse retina demonstrated by AAV-mediated CRISPR/Cas9 knockdown.

We studied the role of sodium/proton exchanger 8 (NHE8) in retinal pigment epithelium (RPE) and photoreceptor cells of adult mouse retina by using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Neisseria meningitidis (Nm). Specific single guide RNAs (sgRNAs) were designed to knockdown the Slc9a8 gene, which encodes the NHE8. Nuclease null NmCas9 and sgRNAs were packaged respectively using adeno-associated viral vector (AAV), and delivered into mouse eyes in vivo by subretinal injection on wild-type mice of about four-week-old when mouse retina is fully developed. Eye samples were collected four weeks after injection for phenotype examination. Real-time PCR analysis demonstrated ∼38% reduction of NHE8 transcripts in retinas injected with AAV-knockdown sgRNA and AAV-Cas9. Loss of photoreceptor cells was found in eyes injected with AAV-knockdown sgRNA and AAV-Cas9 under either the human rhodopsin promoter or the minimal chicken ß-actin promoter, while normal morphology was observed in control eyes injected with AAV-Cas9 and AAV-control sgRNA; immunostaining data showed degenerating photoreceptor cells and RPE cells in eyes injected with knockdown sgRNA and Cas9 AAVs. We further determined that mutant M120K-NHE8 displayed altered intracellular pH regulation in human RPE and primary mouse RPE cells using genetically encoded pH sensor pHluorin and that primary cultured NHE8 mutant RPE cells showed different pH titration curves. These results indicate that NHE8 plays essential function in both RPE and photoreceptor cells. NHE8 dysfunction either in photoreceptor or RPE is sufficient to cause retinal degeneration in adult mice at any age.

Importance of Considering the Middle Capillary Plexus on OCT Angiography in Diabetic Retinopathy.

Purpose: To quantify microvasculature changes in the superficial (SCP), middle (MCP), and deep capillary plexuses (DCP) in diabetic retinopathy (DR). Methods: Retrospective cross-sectional study at a tertiary academic referral center, in which 26 controls (44 eyes), 27 diabetic subjects without retinopathy (44 eyes), 32 subjects with nonproliferative retinopathy (52 eyes), and 27 subjects with proliferative retinopathy (40 eyes) were imaged with optical coherence tomography angiography (OCTA). Outcome measures included parafoveal vessel density (VD), percentage area of nonperfusion (PAN), and adjusted flow index (AFI) at the different plexuses. Results: MCP VD and MCP AFI decreased with worsening DR, while PAN increased, mirroring changes within the DCP. The fitted regression line for MCP and DCP AFI were significantly different than the SCP, while DCP PAN differed from SCP PAN with disease progression. Higher SCP AFI and PAN were different in eyes with diabetes without retinopathy compared with controls. Unexpectedly, sex was found to independently influence MCP VD and AFI with worsening disease. Conclusions: OCTA parameters in the MCP and DCP displayed parallel changes with DR progression, different from the SCP, emphasizing the importance of physiologic considerations in the retinal capillaries. Thus, segmentation protocols that include the MCP within the SCP may be confounded. A difference in DCP PAN with worsening DR was unmasked relative to a prior study that included the MCP with SCP. We confirm that SCP AFI and PAN may serve as early indicators of microvascular changes in DR and identify an interaction between sex and the MCP deserving further study.

CHARACTERIZING PHOTORECEPTOR CHANGES IN ACUTE POSTERIOR MULTIFOCAL PLACOID PIGMENT EPITHELIOPATHY USING ADAPTIVE OPTICS.

PURPOSE: To characterize lesions of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) by multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO). METHODS: We included patients with APMPPE at different stages of evolution of the placoid lesions. Color fundus photography, spectral domain optical coherence tomography, infrared reflectance, fundus autofluorescence, and AOSLO images were obtained and registered to correlate microstructural changes. RESULTS: Eight eyes of four patients (two women) were included and analyzed by multimodal imaging. Photoreceptor reflectivity within APMPPE lesions was more heterogeneous than in adjacent healthy areas. Hyperpigmentation on color fundus photography appeared hyperreflective on infrared reflectance and on AOSLO. Irregularity of the interdigitation zone and the photoreceptor inner and outer segment junctions (IS/OS) on spectral domain optical coherence tomography was associated with photoreceptor hyporeflectivity on AOSLO. Interruption of the interdigitation zone or IS/OS was associated with loss of photoreceptor reflectivity on AOSLO. CONCLUSION: Irregularities in the reflectivity of the photoreceptor mosaic are visible on AOSLO even in inactive APMPPE lesions, where the photoreceptor bands on spectral domain optical coherence tomography have recovered. Adaptive optics scanning laser ophthalmoscopy combined with multimodal imaging has the potential to enhance our understanding of photoreceptor involvement in APMPPE.

Quantifying Microvascular Abnormalities With Increasing Severity of Diabetic Retinopathy Using Optical Coherence Tomography Angiography.

Purpose: We quantified retinal and choriocapillaris microvascular changes in healthy control eyes and different stages of diabetic retinopathy (DR) using optical coherence tomography angiography (OCTA). Methods: This retrospective cross-sectional study included 137 eyes of 86 patients with different stages of DR and 44 eyes of 26 healthy age-matched controls. Participants were imaged with a commercial OCTA device (RTVue-XR Avanti). We analyzed the superficial (SCP) and deep (DCP) retinal capillary plexus, the full retina, and choriocapillaris for the following OCTA parameters: foveal avascular zone, vessel density, percent area of nonperfusion (PAN), and adjusted flow index (AFI). We adjusted for age, sex, and the correlation between eyes of the same study participant in our statistical models. Results: All OCTA parameters showed a significant linear correlation with DR severity (P < 0.05) in the univariate models except for AFI measured in the SCP and these correlations remained significant after correcting for covariates. Compared to the other capillary layers, the AFI at the DCP decreased significantly with DR severity. When comparing individual disease severity groups as categories, eyes of subjects with diabetes without DR had significantly increased PAN and AFI in the SCP compared to healthy subjects (P < 0.05). Conclusions: Retinal and choriocapillaris vascular nonperfusion in OCTA is correlated significantly with disease severity in eyes with DR. Higher flow in the SCP may be an early marker of diabetic microvascular changes before clinical signs of DR. The steep decline of blood flow in the DCP with increasing DR severity suggests that alterations at the DCP warrant further investigation.

Adaptive Optics Scanning Laser Ophthalmoscopy and Multimodal Imaging of Peau D'Orange in Pseudoxanthoma Elasticum.

A 41-year-old male with pseudoxanthoma elasticum who presented with progressive vision loss in his left periphery is discussed. Bilateral angioid streaks, optic disc drusen, choroidal neovascularization, and peau d'orange were present. Imaging of the area with peau d'orange with adaptive optics scanning laser ophthalmoscopy and en face optical coherence tomography at Bruch's membrane (BM) revealed a pattern identical to the patches of peau d'orange visible with conventional fundus imaging techniques. These results show that structural abnormalities at the level of BM, likely a result of calcification, correlate with the characteristic "orange peel" pattern known as peau d'orange. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:436-440.].