ABSTRACT
OBJECTIVES: Preeclampsia (PE) is a severe complication of pregnancy characterized by hypertension, proteinuria and compromised fetal blood supply. The eye, like other end organs, is affected by this systemic condition, but unlike in other organs, ocular media transparency allows high-resolution optical visualization of the vascular structure of the retina. Our aim was to assess how ultrasound-determined ocular blood-flow correlates with vascular structure of the retina and choriocapillaris determined by optical coherence tomography angiography (OCTA). METHODS: Plane-wave ultrasound and OCTA were performed on both eyes of 40 consecutive subjects consisting of normal controls (n = 11), mild PE (n = 5), severe PE (n = 17) and chronic or gestational hypertension (n = 7) within 72 hours following delivery. From ultrasound, we measured pulsatile flow velocity and resistance indices in the central retinal artery (CRA) and vein, the short posterior ciliary arteries (SPCAs) and choroid. From OCTA, we measured vascular density (VD) in the superficial, deep retina and choriocapillaris. We determined differences in Doppler and OCTA parameters among groups and correlations between ultrasound and OCTA. RESULTS: In severe PE, flow resistance was reduced with respect to controls. Flow velocity and resistance in the and SPCA were moderately correlated with VD in the choriocapillaris and peripapillary retina, but VD in PE did not differ significantly from controls. CONCLUSIONS: Although OCTA parameters were moderately correlated with Doppler ultrasound, OCTA did not demonstrate significant differences between PE and controls postpartum.
Subject(s)
Pre-Eclampsia , Retinal Vessels , Female , Pregnancy , Humans , Retinal Vessels/diagnostic imaging , Fluorescein Angiography/methods , Tomography, Optical Coherence/methods , Pre-Eclampsia/diagnostic imaging , Ultrasonography, DopplerABSTRACT
The American Academy of Ophthalmology evaluated the practice of routine screening for intraocular infection from Candida septicemia. In the United States, ophthalmologists are consulted in the hospital to screen for intraocular infection routinely for patients with Candida bloodstream infections. This practice was established in the era before the use of systemic antifungal medication and the establishment of definitions of ocular disease with candidemia. A recent systematic review found a rate of less than 1% of routinely screened patients with endophthalmitis from Candida septicemia. Other studies found higher rates of endophthalmitis but had limitations in terms of inaccuracies in ocular disease classification, lack of vitreous biopsies, selection biases, and lack of longer-term visual outcomes. Some studies attributed ocular findings to Candida infections, rather than other comorbidities. Studies also have not demonstrated differences in medical management that are modified for eye disease treatment; therefore, therapy should be dictated by the underlying Candida infection, rather than be tailored on the basis of ocular findings. In summary, the Academy does not recommend a routine ophthalmologic consultation after laboratory findings of systemic Candida septicemia, which appears to be a low-value practice. An ophthalmologic consultation is a reasonable practice for a patient with signs or symptoms suggestive of ocular infection regardless of Candida septicemia.
Subject(s)
Academies and Institutes/standards , Candidemia/diagnosis , Endophthalmitis/diagnosis , Eye Infections, Fungal/diagnosis , Ophthalmology/organization & administration , Practice Guidelines as Topic , Candidemia/microbiology , Endophthalmitis/microbiology , Eye Infections, Fungal/microbiology , Humans , Incidence , Risk Factors , United StatesABSTRACT
OBJECTIVE: Severe preeclampsia complicates roughly 1% of all pregnancies. One defining feature of severe preeclampsia is new onset visual disturbance. The accessibility of the choroid to high-resolution, noninvasive imaging makes it a reasonable target of investigation for disease prediction, stratification, or monitoring in preeclampsia. This study aimed to compare subfoveal choroidal thickness between women with severe preeclampsia and those with normotensive pregnancies, and to investigate associations between such findings and other indicators of disease severity, including gestational age and serum angiogenic factors. STUDY DESIGN: We designed a case-control study comprised of 36 women diagnosed with severe preeclampsia (cases) matched to 37 normotensive women (controls) by race/ethnicity and parity, all diagnosed in the postpartum period. All patients underwent enhanced depth imaging spectral-domain optical coherence tomography and serum analysis. RESULTS: Cases showed no difference in subfoveal choroidal thickness compared with controls (p = 0.65). Amongst cases, subfoveal choroidal thickness and gestational age at delivery were inversely related (r = 0.86, p < .001). There was a positive association of placental growth factor with subfoveal choroidal thickness amongst cases (r = 0.54, p = 0.002). CONCLUSION: This study suggests a relationship between the degree of disease severity and the magnitude of choroidal thickening. We also show an association between this index and placental growth factor level in the postpartum period.
Subject(s)
Choroid/pathology , Placenta Growth Factor/blood , Postpartum Period/blood , Pre-Eclampsia/pathology , Adult , Case-Control Studies , Female , Humans , Linear Models , Pregnancy , Severity of Illness Index , Tomography, Optical Coherence/methodsABSTRACT
Over 800 mutations in the ABCA4 gene cause autosomal recessive Stargardt disease. Due to extensive genetic heterogeneity, observed variant-associated phenotypes can manifest tremendous variability of expression. Furthermore, the high carrier frequency of pathogenic ABCA4 alleles in the general population (~1:20) often results in pseudo-dominant inheritance patterns further complicating the diagnosis and characterization of affected individuals. This study describes a genotype/phenotype analysis of an unusual family with multiple macular disease phenotypes spanning across two generations and segregating four distinct ABCA4 mutant alleles. Complete sequencing of ABCA4 discovered two known missense mutations, p.C54Y and p.G1961E. Array comparative genomic hybridization revealed a large novel deletion combined with a small insertion, c.6148-698_c.6670del/insTGTGCACCTCCCTAG, and complete sequencing of the entire ABCA4 genomic locus uncovered a new deep intronic variant, c.302+68C>T. Patients with the p.G1961E mutation had the mildest, confined maculopathy phenotype with peripheral flecks while those with all other mutant allele combinations exhibited a more advanced stage of generalized retinal and choriocapillaris atrophy. This family epitomizes the clinical and genetic complexity of ABCA4-associated diseases. It contained variants from all classes of mutations, in the coding region, deep intronic, both single nucleotide variants and copy number variants that accounted for varying phenotypes segregating in an apparent dominant fashion. Unequivocally defining disease-associated alleles in the ABCA4 locus requires a multifaceted approach that includes advanced mutation detection methods and a thorough analysis of clinical phenotypes.
Subject(s)
ATP-Binding Cassette Transporters/genetics , Macula Lutea/pathology , Macular Degeneration/congenital , Mutation , Phenotype , Adult , Aged , Comparative Genomic Hybridization , DNA Copy Number Variations , Electroretinography , Female , High-Throughput Nucleotide Sequencing , Humans , Macular Degeneration/genetics , Macular Degeneration/physiopathology , Male , Middle Aged , Pedigree , Stargardt DiseaseSubject(s)
COVID-19 , Pandemics , Humans , Inpatients , Lung , Referral and Consultation , SARS-CoV-2 , Transplant RecipientsSubject(s)
Retinal Diseases/physiopathology , Sneezing/physiology , Ultraviolet Rays/adverse effects , Humans , Male , Reflex/physiology , Reflex/radiation effects , Retina/diagnostic imaging , Retina/radiation effects , Retinal Diseases/diagnosis , Sneezing/radiation effects , Tomography, Optical Coherence/methods , Young AdultABSTRACT
PURPOSE: To investigate the incidence of reticular macular disease (RMD), a subphenotype of age-related macular degeneration, in multilobular geographic atrophy (GA) and its relation to GA progression. METHODS: One hundred and fifty-seven eyes of 99 subjects with age-related macular degeneration, primary GA, and good quality autofluorescence, and/or infrared images were classified into unilobular GA (1 lesion) or multilobular GA (≥ 2 distinct and/or coalescent lesions). Thirty-four subjects (50 eyes) had serial imaging. The authors determined the spatiotemporal relationships of RMD to GA and GA progression rates in five macular fields. RESULTS: 91.7% eyes (144 of 157) had multilobular GA, 95.8% of which exhibited RMD. In subjects with serial imaging, the mean GA growth rate significantly differed between the unilobular and multilobular groups (0.40 vs. 1.30 mm2/year, P < 0.001). Of the macular fields in these eyes, 77.1% of fields with RMD at baseline showed subsequent GA progression, while 53.4% of fields without RMD showed progression (P < 0.001). Percentage of fields with RMD significantly correlated with GA progression rate (P = 0.01). CONCLUSION: Autofluorescence and infrared imaging demonstrates that RMD is nearly always present with multilobular GA in age-related macular degeneration. Furthermore, GA lobules frequently develop in areas of RMD, suggesting progression of a single underlying disease process.
Subject(s)
Geographic Atrophy/complications , Retinal Dystrophies/etiology , Retinal Pigment Epithelium/pathology , Aged, 80 and over , Disease Progression , Female , Fluorescein Angiography , Follow-Up Studies , Geographic Atrophy/classification , Geographic Atrophy/diagnosis , Humans , Macular Degeneration/complications , Macular Degeneration/diagnosis , Male , Multimodal Imaging , Ophthalmoscopy , Retinal Drusen/diagnosis , Retinal Dystrophies/diagnosisABSTRACT
PURPOSE: To assess the agreement between color fundus photographs (CFP) and fundus autofluorescence (FAF) images when measuring geographic atrophy (GA) area and reproducibility of measurements between graders. Frequency and disagreement types were also determined. METHODS: Eyes with GA secondary to age-related macular degeneration had CFP and FAF imaging on the same day. Seventy-two eyes from 72 patients were included in the analysis. Three graders calculated GA area using digital imaging software. Main outcome measures included agreement between graders for GA area on both FAF and CFP and agreement between both imaging modalities. RESULTS: The intraclass correlation for the 3 graders for FAF images was 0.99 (95% confidence interval, 0.98-0.99). For CFP, it was 0.96 (95% confidence interval, 0.94-0.97). The intraclass correlation between imaging modalities for Graders 1, 2, and 3 were 0.93, 0.85, and 0.87, respectively. Sensitivities to detect involvement of fovea (CFP, 86-97%; FAF, 72-93%) and specificities to detect sparing of fovea (CFP, 74-76%; FAF, 59-88%) overlapped between imaging modalities. CONCLUSION: Both CFP and FAF imaging are reliable for measuring GA area. Interobserver agreement was slightly higher for FAF images. Although the high agreement between modalities suggests that either would be appropriate for measuring GA area, using both may be the best approach for following GA progression.
Subject(s)
Fluorescein Angiography , Geographic Atrophy/diagnosis , Photography , Aged , Aged, 80 and over , Female , Fundus Oculi , Geographic Atrophy/etiology , Humans , Macular Degeneration/complications , Male , Middle Aged , Observer Variation , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
PURPOSE: To describe the first known case of an extracorporeal membrane oxygenation (ECMO)-related complication in an adult. METHODS: Case report. RESULTS: A 34-year-old man awaiting a lung transplant for interstitial lung disease was connected to an ECMO circuit as a bridge to lung transplant, with a drainage catheter attached to his right internal jugular vein. Shortly after he was cannulated, he developed blurred vision in his right eye and was found to have a progressively worsening bullous exudative retinal detachment. After receiving a lung transplant and getting decannulated from ECMO, his bullous detachment rapidly improved. The patient's clinical course as well as his ophthalmic testing showed findings inconsistent with alternative diagnoses such as central serous chorioretinopathy. His findings were best explained as a complication of ECMO cannulation. CONCLUSION: Extracorporeal membrane oxygenation may be associated with bullous exudative retinal detachment in rare cases where there is a possible anatomical or physiological predisposition.
Subject(s)
Extracorporeal Membrane Oxygenation , Retinal Detachment , Adult , Extracorporeal Membrane Oxygenation/adverse effects , Humans , Male , Retinal Detachment/diagnosis , Retinal Detachment/etiologyABSTRACT
PURPOSE: Fundus autofluorescence imaging has been shown to be helpful in predicting progression of geographic atrophy (GA) secondary to age-related macular degeneration. We assess the ability of fundus autofluorescence imaging to predict rate of GA progression using a simple categorical scheme. METHODS: Subjects with GA secondary to age-related macular degeneration with fundus autofluorescence imaging acquired at least 12 months apart were included. Rim area focal hyperautofluorescence was defined as percentage of the 500-µm-wide margin bordering the GA that contained increased autofluorescence. Rim area focal hyperautofluorescence on baseline fundus autofluorescence images was assessed and categorized depending on the extent of rim area focal hyperautofluorescence (Category 1: ≤33%; Category 2: between 33 and 67%; Category 3: ≥67%). Total GA areas at baseline and follow-up were measured to calculate change in GA progression. RESULTS: Forty-five eyes of 45 subjects were included; average duration of follow-up was 18.5 months. Median growth rates differed among categories of baseline rim area focal hyperautofluorescence (P = 0.01 among Categories 1, 2, and 3; P = 0.008 for Category 1 compared with Category 3, Jonckheere-Terpstra test). CONCLUSION: A simple categorical scheme that stratifies the amount of increased autofluorescence in the 500-µm margin bordering GA may be used to differentiate faster and slower progressors.
Subject(s)
Fluorescein Angiography/methods , Fundus Oculi , Geographic Atrophy/diagnosis , Aged , Disease Progression , Female , Fluorescence , Follow-Up Studies , Humans , Male , Predictive Value of Tests , Time FactorsABSTRACT
PURPOSE: Tacrolimus is a commonly used immunosuppressant medication after lung transplantation. In rare cases, tacrolimus causes a medication-induced optic neuropathy (TON) that can lead to significant vision loss. OBSERVATIONS: In this series, we describe three cases of TON, 1-10 years after medication use. Two patients were young (22yr and 33yr) females with cystic fibrosis. The last case was a 65yr male with idiopathic pulmonary fibrosis. In 2/3 cases tacrolimus serum levels were normal. Visual acuity ranged from 20/20 to 20/300, and vision loss occurred acutely to sub-acutely, over a span of 2-3 months. CONCLUSIONS AND IMPORTANCE: As presented here, TON can be highly variable. MRI findings are often non-specific, from normal brain findings to extensive white matter changes. There remains an unclear association with graft-versus-host disease and reduced kidney function. Visual findings are often subtle, including color vision aberration and peripheral visual field deficits, both of which usually require an ophthalmologic evaluation. When diagnosed in a timely fashion, TON is at least partially reversible in up to half of all cases. While rare, the cases described here support post-lung transplant ophthalmologic evaluation in those taking high-risk medications.
ABSTRACT
PURPOSE: The temporary cessation and profound changes in ophthalmic care delivery that occurred as a result of the coronavirus disease 2019 (COVID-19) pandemic have yet to be fully understood. Our objective is to assess patients' self-reported impact of health care lockdown measures on their fears and anxieties during the crisis period of the COVID-19 pandemic in New York City. METHODS: We conducted a digital, self-reported, patient care survey distributed by an e-mail at Columbia University's Department of Ophthalmology outpatient faculty practice. Inclusion criteria were age greater than or equal to 18 years, a diagnosis of either retinal disease or glaucoma, and a canceled or rescheduled ophthalmology established patient appointment during the acute phase of the COVID-19 pandemic in New York City. Patients without an e-mail address listed in their electronic medical records were excluded. The survey occurred between March 2, 2020, to May 30, 2020. Primary measures were survey responses to assess key areas of patient anxiety or concern during the pandemic including the safety of care delivery in a COVID pandemic, difficulties contacting or being seen by their ophthalmologist, concern of vision loss or disease progression, and concern over missed or access to treatments. Secondary measures were correlating survey response to factors such as visual acuity, intraocular pressure, diagnosis, disease severity, follow-up urgency, recent treatments, and diagnostic testing data. RESULTS: Of the 2594 surveys sent out, 510 (19.66%) were completed. Over 95% of patients were at least as concerned as in normal circumstances about their ocular health during the peak of the pandemic. Overall, 76% of respondents were more concerned than normal that they could not be seen by their ophthalmologist soon enough. Increased concern over ocular health, disease progression, and access to care all showed positive correlations (P<0.05) with worse disease severity as measured with testing such as visual fields and optical coherence tomography. In addition, 55% of patients were afraid of contracting COVID-19 during an office visit. CONCLUSION AND RELEVANCE: We found a majority of our patients were concerned about limitations in access to ophthalmic care and were fearful of disease progression. In addition, we found a number of demographic and clinical factors that correlated with increased anxiety in our patients.
Subject(s)
COVID-19 , Glaucoma , Communicable Disease Control , Humans , Intraocular Pressure , Pandemics , SARS-CoV-2ABSTRACT
The traditional method for documenting and quantifying geographic atrophy (GA) is color photography. This method has been shown to be reproducible in several clinical trials, including the Age-related Eye Disease Study (AREDS) and the natural progression of GA studies by Sunness et al. (AREDS No. 6, Am J Ophthalmol 132(5):668-681, 2001; Sunness et al., Invest Ophthalmol Vis Sci 40(8):1761-1769, 1999). Nevertheless, it can be difficult to distinguish between dead/nonfunctioning retinal pigment epithelium (RPE), living but depigmented RPE (RPE often release melanin granules upon injury), and yellowish coloration caused by large drusen or calcified regressed drusen. Two imaging technologies that seem promising are fundus autofluorescence (FAF) and spectral domain (high resolution) optical coherence tomography (SDOCT). Here we provide an overview of FAF imaging in the setting of age-related macular degeneration (AMD) and GA.
Subject(s)
Diagnostic Imaging/methods , Fundus Oculi , Geographic Atrophy/diagnosis , Disease Progression , Fluorescence , Geographic Atrophy/complications , Geographic Atrophy/pathology , Humans , Retinal Drusen/complications , Retinal Drusen/diagnosis , Retinal Drusen/pathologyABSTRACT
Purpose: Pre-eclampsia (PE) is a serious complication of pregnancy characterized by high blood pressure, proteinuria, compromised fetal blood supply, and potential organ damage. The superficial location of the eye makes it an ideal target for characterization hemodynamics. Our aim was to discern the impact of PE on ocular blood flow. Methods: 18 MHz plane-wave ophthalmic ultrasound scanning was performed on subjects with PE (n = 26), chronic or gestational hypertension (n = 8), and normal controls (n = 19) within 72 hours of delivery. Duplicate three-second long scans of the posterior pole including the optic nerve were acquired at 6000 images/sec for evaluation of the central retinal artery and vein and the short posterior ciliary arteries. The choroid was scanned at 1000 images/sec. Doppler analysis provided values of pulsatile flow velocity and resistance indexes. Results: End diastolic velocity was higher, and pulsatility and resistive indexes were significantly lower in the choroid, central retinal artery and short posterior ciliary arteries in PE than in controls. Blood pressure was elevated in PE with respect to controls and was negatively correlated with resistance. Conclusions: Although vasoconstriction is considered characteristic of PE, we found reduced resistance in the orbital vessels and choroidal arterioles, implying vasodilation at this level. Future studies incorporating optical coherence tomography angiography for characterization of the retina and choriocapillaris in conjunction with plane-wave ultrasound scanning, particularly in late pregnancy, might address this conundrum. Translational Relevance: Use of plane-wave ultrasound scanning for evaluation ocular blood flow in women at risk for PE may offer an avenue towards early detection and clinical intervention.
Subject(s)
Pre-Eclampsia , Retinal Artery , Angiography , Ciliary Arteries/diagnostic imaging , Female , Humans , Pre-Eclampsia/diagnosis , Pregnancy , Retinal Artery/diagnostic imaging , UltrasonographyABSTRACT
Two patients presented with angle closure many years after cataract extraction. The first patient presented with acute intraocular pressure (IOP) elevation and closed iridocorneal angle that resolved with a laser iridotomy. The second patient presented with an insidious course of high IOP and progressive narrowing of the iridocorneal angle, ultimately requiring a pars plana vitrectomy and glaucoma valve implant, with subsequent normalization of pressure and angle anatomy. Although rare, angle closure in eyes with posterior chamber intraocular lenses is a dangerous complication that can occur many years after cataract extraction. Retained lens fragments, and perhaps repeated intravitreal injections, might place susceptible patients at risk.
Subject(s)
Cataract Extraction , Glaucoma, Angle-Closure , Lenses, Intraocular , Anterior Chamber , Glaucoma, Angle-Closure/diagnosis , Glaucoma, Angle-Closure/etiology , Glaucoma, Angle-Closure/surgery , Humans , Intraocular Pressure , VitrectomyABSTRACT
OBJECTIVE: To test in vivo whether spectral domain optical coherence tomography (SD-OCT) provides adequate resolution for reproducible measurement of photoreceptor (PR) layer at the margins of geographic atrophy (GA), and if it delineates the relationship between PR layer and retinal pigment epithelium at the margins of GA. DESIGN: Prospective consecutive case series. PARTICIPANTS: Patients with GA secondary to nonneovascular age-related macular degeneration (AMD) identified during routine follow-up at Duke Eye Center between January 3, 2006, and June 3, 2007, and who consented to participate in this study. METHODS: We used SD-OCT to image eyes. Multiple B-scans from each eye were saved and independently graded by 2 graders and the following locations were marked: (1) site where PR thickness began to decline below its baseline, (2) site where PR layer disappeared, and (3) site of the GA margin. These data were processed to calculate the locations of PR losses relative to GA margins and were categorized as (A) bridging across GA margins, (B) entirely within GA margins, or (C) entirely outside GA margins. MAIN OUTCOME MEASURES: Location of PR loss (bridging across GA margins, entirely within GA margins, or entirely outside GA margins) was calculated. Distances from the GA margin were measured for beginning and ending of PR loss. Interobserver agreement was determined for categories of PR loss as well as locations of PR loss relative to the GA margin. RESULTS: We analyzed 500 unique scans. The PR loss occurred most frequently bridging across the GA margin (65% scans), second most frequently entirely inside the GA margin (29% scans), and least frequently entirely outside the GA margin (6% scans). Loss of PR started an average of 61 microm (standard deviation [SD] +/- 235) outside the GA margin, ended an average of 311+/-273 microm inside the GA margin, and spanned an average of 372+/-179 microm. CONCLUSIONS: Relative to GA margins in non-neovascular AMD with GA, SD-OCT provides adequate resolution for quantifying PR loss. It may also serve as a means of tracking disease progression in future interventional trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
Subject(s)
Macular Degeneration/diagnosis , Photoreceptor Cells, Vertebrate/pathology , Retinal Pigment Epithelium/pathology , Tomography, Optical Coherence , Aged , Aged, 80 and over , Atrophy , Female , Humans , Male , Middle Aged , Observer Variation , Prospective Studies , Reproducibility of ResultsABSTRACT
PURPOSE: The purpose of this study is to document the appearance of macular toxoplasmosis scars with the high-resolution cross-sectional retinal imaging technique of optical coherence tomography (OCT) and investigate whether a correlation exists between the morphology of the toxoplasmosis scars, the OCT images, and visual acuity. METHODS: In this retrospective observational case series, fundus photos were taken of the macular lesions that were also documented by OCT. Photos were digitized for the purpose of sizing lesions. All images were classified by the authors. RESULTS: There were 10 consecutive patients (13 eyes) whose average age is 13.0 years. Macular lesions ranged from 1.6 mm2 to 20.2 mm2. OCT features included retinal thinning, retinal pigment epithelial hyperreflectivity, excavation, intraretinal cysts, and fibrosis. Patients with better than expected vision had either parafoveal lesions or an intact neurosensory layer. CONCLUSION: The most characteristic OCT features in this young population were prominent retinal thinning, retinal pigment epithelium hyperreflectivity, and excavation of varying severity. OCT imaging is helpful in explaining better than expected vision.
Subject(s)
Choroid Diseases/diagnosis , Macula Lutea/pathology , Retinal Diseases/diagnosis , Tomography, Optical Coherence/methods , Toxoplasmosis, Ocular/congenital , Toxoplasmosis, Ocular/diagnosis , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Male , Retrospective Studies , Visual Acuity , Young AdultABSTRACT
Background: The extensive phenotypic heterogeneity of monogenic diseases can be largely traced to intragenic variation; however, recent advances in clinical detection and gene sequencing have uncovered the emerging role of non-allelic variation (i.e. genetic trans-modifiers) in shaping disease phenotypes. Identifying these associations are not only of significant diagnostic value, but also provides scientific insight into the expanded molecular etiology of rare diseases. This reports describes the discordant clinical manifestation of a family segregating mutations in ABCA4 and PROM1. Methods: Three patients across a two generation family underwent multimodal imaging and functional testing of the retina including color photography, fundus autofluorescence (AF), spectral domain-optical coherence tomography (SD-OCT) and full-field electroretinography (ffERG). Genetic characterization was carried out by direct Sanger and whole exome sequencing. Results: Clinical examination revealed similar retinal degenerative phenotypes in the proband and her mother. Despite being younger, the proband's phenotype was more advanced and exhibited additional features related to Stargardt disease not found in the mother. Whole exome sequencing identified a pathogenic missense variant in PROM1, c.400C > T, p.(Arg134Cys), as the underlying cause of retinal disease in both the proband and mother. Sequencing of the ABCA4 locus uncovered a single disease-causing variant, c.5714 + 5G > A in the daughter segregating from the father who, surprisingly, also exhibited very subtle disease changes associated with STGD1 despite being a heterozygous carrier. Conclusions: Harboring an additional heterozygous ABCA4 mutation increases severity and confers STGD1-like features in patients with PROM1 disease which provides supporting evidence for their shared pathophysiology and potential treatment prospects.
Subject(s)
AC133 Antigen/genetics , ATP-Binding Cassette Transporters/genetics , Macular Degeneration/pathology , Mutation , Retinal Degeneration/pathology , Stargardt Disease/pathology , Adolescent , Adult , Aged , Aged, 80 and over , Case-Control Studies , Female , Follow-Up Studies , Humans , Macular Degeneration/genetics , Male , Middle Aged , Pedigree , Phenotype , Prognosis , Retinal Degeneration/genetics , Stargardt Disease/genetics , Young AdultABSTRACT
PURPOSE: To evaluate the response of eyes treated with photodynamic therapy (PDT) for predominantly hemorrhagic lesions in neovascular age-related macular degeneration (NVAMD). DESIGN: Consecutive, interventional case series. METHODS: A retrospective review was conducted of eyes with NVAMD that were treated with PDT for predominantly hemorrhagic subfoveal lesions. Baseline data recorded were patient age, use of aspirin or warfarin, history of previous PDT treatment, visual acuity (VA), extent of subretinal hemorrhage (SRH), and central foveal thickness (CFT) and total macular volume (TMV) measured by optical coherence tomography (OCT). Follow-up VA, SRH status, and complications were recorded. RESULTS: Twenty-one eyes of 21 patients were identified with a mean posttreatment follow-up of 9.4 months. Mean pretreatment VA was 20/210, and mean SRH size was 16 disk areas. The SRH resolved in 18 eyes (86%) after a mean of six months, with a mean VA of 20/210. Mean VA for all eyes at most recent follow-up was 20/250. Thirteen (62%) of 21 eyes exhibited stable or improved VA at the most recent follow-up. VA one year after PDT inversely correlated with patient age (P = .045) and initial SRH size (P = .04) and positively correlated with pretreatment VA (P = .01). Previous PDT treatment, use of aspirin or warfarin, and OCT data did not significantly correlate with VA or SRH resolution. CONCLUSIONS: PDT may be an effective treatment for minimizing visual loss in eyes with NVAMD and predominantly hemorrhagic lesions. Further study is warranted to detail the risk-benefit ratio and compare PDT with other treatment modalities.