Case Report: Pentosan Polysulfate Sodium Maculopathy Originally Diagnosed as Pattern Macular Dystrophy.

Near-infrared and Short-wavelength Autofluorescence in Resolved Central Serous Chorioretinopathy: Association With Outer Retinal Layer Abnormalities

Severe bilateral retinal degeneration following a twenty-six-year pentosan polysulfate sodium exposure: a case report

PurposeTo report near-infrared reflectance (NIR-R), near-infrared autofluorescence (NIR-AF) and blue wave autofluorescence (BW-AF) appearance of choroidal nevi using a confocal scanning laser ophthalmoscope (cSLO).Patients and methodsNIR-R, NIR-AF and BW-AF images of choroidal nevi were compared with color fundus photos (CF). Images were graded as hyperreflective if reflectance was much greater than background, hyporeflective if less than background, and isoreflective if the same as the background.ResultsForty-two nevi of 39 patients were imaged. When compared with CF, nevi could be identified on 95% (40/42) NIR-R images (95% CI: 83.5-99.3). On NIR-R 71% (30/42) demonstrated hyperreflectance and 24% (10/42) were hyporeflective. Hyperreflectivity was demonstrated in 96% (23/24) of NIR-AF images (95% CI: 79.1-99.9) and 34% (14/41) of BW-AF images (95% CI: 20.0-50.5). On NIR-R, 29/40 (73%) were apparently smaller in comparison with CF and 11/40 (28%) had the same area. A correlation was found between NIR-R and NIR-AF (P=0.02) but not with BW-AF (P=0.15).ConclusionsNevi can be visualized well using NIR-R and NIR-AF imaging modalities, but are less frequently visible using BW-AF. These changes may be related to melanin within the choroid or chronic changes of the overlying retinal pigment epithelium.

Introduction Variants in the RCBTB1 gene have recently been described in patients with inherited retinal disease; so far, there is limited knowledge about this entity, differential diagnoses, and disease progression. Here, we report a novel splice variant in RCBTB1 and describe the associated retinopathy. Methods Clinical assessment included multimodal imaging with optical coherence tomography, blue-light fundus autofluorescence, and near-infrared fundus autofluorescence. Atrophy progression was evaluated over time. Genetic testing was conducted by next-generation sequencing, pathogenicity was assessed by in silico analysis. Results A 54-year-old woman presented with a best-corrected visual acuity of 20/50 in the right and 20/63 in the left eye, respectively. Fundus examination showed macular and peripapillary atrophy with foveal sparing, as well as granular alterations extending to the mid-peripheral retina. Genetic testing revealed a novel splice variant (c.1325-2A>G) in intron 11 of RCBTB1. Discussion We confirm that RCBTB1-associated retinal dystrophy shares phenotypic similarities with mitochondrial retinopathy. Multimodal retinal imaging is vital to assess disease progression and may facilitate a better understanding of this pathology.

Purpose: Advancements in retinal imaging have augmented our understanding of the pathology and structure-function relationships of retinal disease. No single diagnostic test is sufficient; rather, diagnostic and management strategies increasingly involve the synthesis of multiple imaging modalities. Methods: This literature review and editorial offer practical clinical guidelines for how the retina specialist can use multimodal imaging to manage retinal conditions. Results: Various imaging modalities offer information on different aspects of retinal structure and function. For example, optical coherence tomography (OCT) and B-scan ultrasonography can provide insights into the microstructural anatomy; fluorescein angiography (FA), indocyanine green angiography (ICGA), and OCT angiography (OCTA) can reveal vascular integrity and perfusion status; and near-infrared reflectance and fundus autofluorescence (FAF) can characterize molecular components within tissues. Managing retinal vascular diseases often includes fundus photography, OCT, OCTA, and FA to evaluate for macular edema, retinal ischemia, and the secondary complications of neovascularization (NV). OCT and FAF play a key role in diagnosing and treating maculopathies. FA, OCTA, and ICGA can help identify macular NV, posterior uveitis, and choroidal venous insufficiency, which guides treatment strategies. Finally, OCT and B-scan ultrasonography can help with preoperative planning and prognostication in vitreoretinal surgical conditions. Conclusions: Today, the retina specialist has access to numerous retinal imaging modalities that can augment the clinical examination to help diagnose and manage retinal conditions. Understanding the capabilities and limitations of each modality is critical to maximizing its clinical utility.

Chapter 7 - Ophthalmic phenotyping: Imaging

To describe the multimodal imaging findings of subretinal hyperreflective exudation (SHE) observed in association with choroidal neovascularization and to distinguish SHE from other forms of subretinal hyperreflective material (SHM) seen in patients with age-related macular degeneration and other macular disorders. A retrospective study on 46 eyes of 42 patients with SHE associated with Types 1, 2, and 3 choroidal neovascularization secondary to neovascular age-related macular degeneration. Patients were examined using multimodal imaging, including color photography, near-infrared reflectance imaging, spectral domain optical coherence tomography, fluorescein angiography, fundus autofluorescence imaging, and indocyanine green angiography. Clinical and imaging characteristics were evaluated at baseline, after the initiation of intravitreal antivascular endothelial growth factor therapy, and during the resolution of SHE. Forty-five of the 46 eyes were treatment naive. The mean ± SD age at the first detection of SHE was 77.2 ± 10.1 years. The mean ± SD follow-up was 2.1 ± 0.6 years. Fluorescein angiography was performed in 42 eyes and demonstrated leakage and/or staining of underlying or adjacent choroidal neovascularization but not of the SHE itself in all eyes. On fluorescein angiography, SHE was transparent in 29 eyes and blocking in 7 eyes. In 32 eyes, SHE showed isoautofluorescence on fundus autofluorescence imaging, and in 8 eyes, SHE showed varying degrees of hyperautofluorescence. Indocyanine green angiography was performed in eight eyes and demonstrated hyperfluorescence of SHE in seven eyes. In eight eyes, SHE was the only evidence of neovascular activity. All eyes having follow-up (42 eyes) showed resolution of the subretinal material with partial or full reconstitution of the ellipsoid zone after a median of 2 injections range (1-16 injections). Subretinal hyperreflective exudation persisted for a median of 9 weeks (range, 4-60 weeks) after the initiation of treatment. The mean visual acuity before treatment was 0.619 (20/83), and it improved to 0.380 (20/48) (P = 0.03) after the resolution of SHE. Subretinal hyperreflective exudation differs from other types of SHM based on the findings from multimodal imaging. This novel type of SHM likely represents a sign of active neovascular age-related macular degeneration distinct from subretinal fluid, hemorrhage, neovascular tissue, lipid, pigment hyperplasia, subretinal fibrosis, and the SHM observed with acquired vitelliform lesions. Intravitreal antivascular endothelial growth factor agents can be used to successfully resolve SHE, often resulting in better visual outcomes in eyes manifesting this form of exudation.

Dos casos de retinopatía externa oculta zonal aguda: importancia del diagnóstico multimodal

Fundus Autofluorescence Patterns in Best Vitelliform Macular Dystrophy

To identify the fundus autofluorescence (FAF) patterns in Best vitelliform macular dystrophy (VMD). Patients affected by VMD in vitelliform, pseudohypopyon, and vitelliruptive stages underwent a complete ophthalmological examination, including best-corrected visual acuity (BCVA), short-wavelength FAF (SW-FAF), near-infrared FAF (NIR-FAF) and microperimetry. the identification of the correlation between SW-FAF and NIR-FAF patterns of the foveal region with BCVA, and central retinal sensitivity in eyes affected by VMD. The secondary outcomes included the definition of the frequency of foveal patterns on SW-FAF and NIR-FAF. Thirty-seven of 64 (58%), 8 of 64 (12.5%) and 19 of 64 (29.5%) eyes showed vitelliform, pseudohypopyon, and vitelliruptive stages respectively. Three main FAF patterns were identified on both techniques: hyper-autofluorescent pattern, hypo-autofluorescent pattern, and patchy pattern. BCVA was significantly different in eyes with hypo-autofluorescent and patchy patterns with respect to eyes showing a hyper-autofluorescent pattern. Similar differences were registered in the FS according to SW-FAF classification. However, the FS differed in each subgroup in the NIR-FAF analysis. Subgroup analyses were performed on the patchy pattern, combining FAF and fundus abnormalities. Considering both FAF techniques, the BCVA differed between the vitelliform and pseudohypopyon stages, and between the vitelliform and vitelliruptive stages. In the NIR-FAF classification, there was a significant statistical difference in the FS between each subgroup; in the SW-FAF, there was a significant difference between the vitelliform and pseudohypopyon stages and the vitelliform and vitelliruptive stages. Three main FAF patterns can be identified in VMD. The patchy pattern is the most frequent, accounting for 70% of eyes on SW-FAF and 80% of eyes on NIR-FAF. A tighter correlation links the classification of NIR-FAF patterns and FS. Longitudinal investigations are warranted to evaluate the course of FAF patterns and their role in disease monitoring.

PurposeWe sought to determine whether information revealed from the reflectance, autofluorescence, and absorption properties of RPE cells situated posterior to reticular pseudodrusen (RPD) could provide insight into the origins and structure of RPD.MethodsRPD were studied qualitatively by near-infrared fundus autofluorescence (NIR-AF), short-wavelength fundus autofluorescence (SW-AF), and infrared reflectance (IR-R) images, and the presentation was compared to horizontal and en face spectral domain optical coherence tomographic (SD-OCT) images. Images were acquired from 23 patients (39 eyes) diagnosed with RPD (mean age 80.7 ± 7.1 [SD]; 16 female; 4 Hispanics, 19 non-Hispanic whites).ResultsIn SW-AF, NIR-AF, and IR-R images, fundus RPD were recognized as interlacing networks of small scale variations in IR-R and fluorescence (SW-AF, NIR-AF) intensities. Darkened foci of RPD colocalized in SW-AF and NIR-AF images, and in SD-OCT images corresponded to disturbances of the interdigitation (IZ) and ellipsoid (EZ) zones and to more pronounced hyperreflective lesions traversing photoreceptor-attributable bands in SD-OCT images. Qualitative assessment of the outer nuclear layer (ONL) revealed thinning as RPD extended radially from the outer to inner retina. In en face OCT, hyperreflective areas in the EZ band correlated topographically with hyporeflective foci at the level of the RPE.ConclusionsThe hyperreflective lesions corresponding to RPD in SD-OCT scans are likely indicative of degenerating photoreceptor cells. The darkened foci at positions of RPD in NIR-AF and en face OCT images indicate changes in the RPE monolayer with the reduced NIR-AF and en face OCT signal suggesting a reduction in melanin that could be accounted for by RPE thinning.

In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the authors detailed macular retinal pigment epithelial abnormalities in six patients. In this paper, a retrospective study of a larger patient pool at one large tertiary retina practice was undertaken to evaluate patients taking PPS and their macular findings. A retrospective chart review was performed on all patients presenting to a single large retina practice between 2011 and 2019. Patient's macular diagnosis, findings, optical coherence tomography scans, and macular auto-fluorescent scans were assessed. This project was Institutional Review Board (IRB) approved by the St Luke's Hospital IRB board (St Louis, MO, USA). Fifty-five patients were identified as taking PPS for IC. Fifty-three patients were found to have a diagnosis consistent with changes attributable to known macular diseases to include macular degeneration and pattern dystrophies. Two (4%) of fifty-five patients had macular findings suggestive of PPS toxicity. The first was a 58-year-old female with subtle retinal pigment epithelium (RPE) deposits on optical coherence tomography that exhibited hyper-autofluorescence. The second was a 72-year-old female with 14 years of PPS use who exhibited RPE excrescences and parafoveal areas of atrophy. Pentosan polysulfate sodium may be the cause of macular findings in a small percentage of patients referred to a tertiary retina practice. Although causation of macular changes with PPS use has yet to be elucidated, clinicians should be aware of this possibility when assessing patients with atypical macular findings. Future longitudinal studies are necessary to evaluate a definitive relationship. This paper should remind all clinicians of the importance of a throughout review of the patient's medication list as novel toxicities may become apparent years after initial FDA trials. The strength of this study is the larger patient population compared to earlier studies, and the main weaknesses include the retrospective nature of the study, lack of family and genetic testing, and lack of multimodal imaging for all patients.

Introduction: Choroidal osteoma is a rare, benign ossifying tumor of the choroid that can present with clinical features overlapping those of inflammatory choroidal lesions. In patients with a history of Vogt-Koyanagi-Harada (VKH) disease, distinguishing between inflammatory relapse and non-inflammatory choroidal pathology can be particularly challenging. This case report highlights the diagnostic pitfalls associated with choroidal osteoma in the setting of prior VKH and underscores the importance of comprehensive multimodal imaging to ensure accurate diagnosis and appropriate management. Case Presentation: A 39-year-old female with a 14-year history of VKH disease, who had been stable off immunosuppressive therapy since 2016, presented in early 2024 with a 7-week history of cloudy vision in the right eye. She was initially diagnosed with a recurrent posterior VKH relapse and treated with high-dose intravenous corticosteroids followed by an oral taper, resulting in symptomatic improvement. However, further multimodal imaging – including wide-field fundus photography, optical coherence tomography (OCT), fundus autofluorescence, OCT angiography, fluorescein angiography, enhanced depth imaging OCT (EDI-OCT), and B-scan ultrasonography – revealed a yellow-orange, minimally elevated subretinal lesion associated with focal choroidal excavation. These findings were consistent with choroidal osteoma and confirmed by EDI-OCT and B-scan ultrasonography. Conclusion: This case illustrates a rare instance of choroidal osteoma masquerading as a posterior relapse of VKH disease. It emphasizes the critical importance of differentiating inflammatory from non-inflammatory choroidal lesions in patients with a history of uveitis. Careful interpretation of multimodal imaging is essential to avoid misdiagnosis, prevent unnecessary immunosuppressive treatment, and reduce associated risks, ultimately leading to improved patient outcomes.

Introduction It was recently proposed that the c.538C>G; p.(Q180E) missense variant in the C1QTNF5 gene leads to autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD). AdGALCD has a phenotypic overlap with other chorioretinal dystrophies but exhibits not the typical characteristics of late-onset retinal degeneration (L-ORD). Here, we report a 70-year-old female simplex patient with adGALCD. Methods Comprehensive ophthalmic examinations included visual field testing and multimodal retinal imaging with optical coherence tomography (OCT), short-wavelength-, and near-infrared fundus autofluorescence. Genetic testing was performed using whole exome sequencing. Results The patient presented with bilateral progressive concentric visual field defects and photophobia for about 8 years. Best corrected visual acuity was 20/40 in the right and 20/32 in the left eye, respectively. On fundus examination, symmetric areas of large peripheral and peripapillary chorioretinal atrophy with foveal sparing were observed with corresponding visual field defects. Fundus autofluorescence imaging showed a central island of preserved autofluorescence surrounded by an extinguished signal in the atrophic areas. OCT imaging showed preserved central retinal pigment epithelium and ellipsoid zone with peripapillary and peripheral atrophy of both layers. Genetic testing revealed a heterozygous missense variant p.(Q180E) in the C1QTNF5 gene. Discussion We confirm that the c.538C>G; p.(Q180E) missense variant in the C1QTNF5 gene may lead to adGALCD.

To determine the fundus autofluorescence (FAF) lifetimes and spectral characteristics of individual drusen and hyperpigmentation independent of those with retinal pigment epithelium (RPE) in geographic atrophy (GA) areas in late-stage age-related macular degeneration (AMD). Three consecutive patients with complete RPE and outer retinal atrophy (cRORA) exhibiting drusen that were calcified or associated with hyperpigmentation were investigated with multimodal non-invasive ophthalmic imaging including colour fundus photography (CFP), optical coherence tomography (OCT), near-infrared reflectance (NIR), blue FAF and fluorescence lifetime imaging ophthalmoscopy (FLIO). Fluorescence lifetimes were measured in two spectral channels (short-wavelength spectral channel (SSC): 500-560 nm and long-wavelength spectral channel (LSC): 560-720 nm). Drusen lacking RPE coverage, as confirmed by CFP and OCT, had longer FAF lifetimes than surrounding cRORA by 127 ± 66 ps (SSC) and 113 ± 48 ps (LSC, both p = 0.008 in Wilcoxon test, N = 9) and by 209 ± 100 ps (SSC) and 121 ± 56 ps (LSC, p < 0.001, N = 14) in two patients. Hyperpigmentation in CFP in a third patient shows strong FAF with prolonged lifetimes. In the SSC, persistent FAF was found inside cRORA. A crescent-shaped hyperfluorescence in an area of continuous RPE but lacking outer retina was seen in one eye with a history of anti-VEGF treatment. Short-wavelength fluorescence in cRORA points to fluorophores beyond RPE organelles. Fluorescence properties of drusen within cRORA differ from invivo drusen covered by RPE. These limited findings from three patients give new insight into the sources of FAF that can be further elucidated in larger cohorts.