FROM DRUSEN TO TYPE 3 MACULAR NEOVASCULARIZATION.

PURPOSE: To investigate the imaging features preceding the occurrence of type 3 (T3) macular neovascularization (MNV) using tracked spectral-domain optical coherence tomography. METHOD: From a cohort of eyes with T3 MNV and ≥ 12 months of previously tracked spectral-domain optical coherence tomography, T3 lesions that developed above soft drusen were selected for optical coherence tomography analysis. Retinal imaging findings at the location where type T3 MNV occurred were analyzed at each follow-up until the onset of T3 MNV. The following optical coherence tomography parameters were assessed: drusen size (height and width), outer nuclear layer/Henle fiber layer thickness at the drusen apex, and the presence of intraretinal hyperreflective foci, retinal pigment epithelium disruption, incomplete retinal pigment epithelium and outer retina atrophy, and complete retinal pigment epithelium and outer retina atrophy. RESULTS: From a cohort of 31 eyes with T3 MNV, T3 lesions developed above soft drusen in 20 eyes (64.5%). Drusen showed progressive growth ( P < 0.001) associated with outer nuclear layer/Henle fiber ( P < 0.001) thinning before T3 MNV. The following optical coherence tomography features were identified preceding the occurrence of T3 MNV, typically at the apex of the drusenoid lesion: disruption of the external limiting membrane/ellipsoid zone and/or the retinal pigment epithelium, hyperreflective foci, and incomplete retinal pigment epithelium and outer retina atrophy/complete retinal pigment epithelium and outer retina atrophy. CONCLUSION: The results demonstrate specific anatomic alterations preceding the occurrence of T3 MNV that most commonly originates above soft drusen. Drusen growth, reduced outer nuclear layer/Henle fiber thickness, and retinal pigment epithelium atrophy at the drusen apex precede the development of T3 MNV. Identifying these optical coherence tomography features should warrant close monitoring for identification of T3 MNV, which can benefit from prompt intravitreal anti-vascular endothelial growth factor therapy.

CENTRAL BOUQUET HEMORRHAGE: Clinical and Multimodal Imaging Features.

PURPOSE: To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage." METHODS: Retrospective, observational, multicenter case series of eyes with central bouquet hemorrhage. Multimodal imaging features were reviewed and analyzed. RESULTS: Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6 ± 21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia Type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with central bouquet hemorrhage displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer. Cross-sectional optical coherence tomography showed a well-delineated round hyperreflective lesion involving the central foveal Henle fiber layer/outer nuclear layer in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented Henle fiber layer were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36). CONCLUSION: "Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with Henle fiber layer hemorrhage and encountered in a spectrum of macular disease.

PUNCTATE INNER PACHYCHOROIDOPATHY: Demographic and Clinical Features of Inner Choroidal Inflammation in Eyes with Pachychoroid Disease.

PURPOSE: To perform an unsupervised machine learning clustering of patients with punctate inner choroidopathy (PIC) and provide new insights into the significance of pachychoroid disease features in PIC eyes. METHODS: Retrospective multicenter study, including 102 eyes from 82 patients diagnosed with PIC. Demographics, clinical data, and multimodal imaging, including fundus photography, optical coherence tomography, and indocyanine green angiography, were collected. Clusters of eyes were identified, and multilevel logistic regression analysis was performed to compare between-group differences. RESULTS: Using 17 clinical features, two distinct clusters of patients with PIC were identified. Cluster 1 patients were characterized by older age, high myopia, myopic maculopathy features, thin choroids, multiple lesions, and a higher likelihood of developing patchy chorioretinal atrophy. Cluster 2 consisted of younger age, emmetropia or low myopia, thick choroids, choroidal vascular hyperpermeability on late-phase indocyanine green angiography, and high prevalence of focal choroidal excavation. These features exhibited significant differences ( P < 0.05) between the two clusters. CONCLUSION: While PIC typically affects young myopic female patients with thin choroids, a subset of patients with PIC exhibits features associated with pachychoroid disease. Considering the potential influence of choroidal venous insufficiency on PIC manifestations and secondary complications, we propose the term "punctate inner pachychoroidopathy" to characterize this distinct subtype of PIC.

INFLAMMATORY CELL ACTIVITY IN TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Histologic Case Study.

BACKGROUND: Imaging indicators of macular neovascularization risk can help determine patient eligibility for new treatments for geographic atrophy secondary to age-related macular degeneration. Because type 1 macular neovascularization includes inflammation, we assessed by histology the distribution of cells with inflammatory potential in two fellow eyes with age-related macular degeneration. METHODS: Two eyes of a White woman in her 90's with type 3 macular neovascularization treated with antivascular endothelial growth factor were prepared for high-resolution histology. Eye-tracked spectral domain optical coherence tomography applied to the preserved donor eyes linked in vivo imaging to histology. Cells were enumerated in the intraretinal, subretinal, and subretinal retinal pigment epithelium (RPE)-basal lamina compartments on 199 glass slides. Cells with numerous organelles were considered to RPE-derived; cells with sparse RPE organelles were considered non-RPE phagocytes. RESULTS: Both eyes had soft drusen and abundant subretinal drusenoid deposit. In the retina and subretinal space, RPE-derived cells, including hyperreflective foci, were common (n = 125 and 73, respectively). Non-RPE phagocytes were infrequent (n = 5 in both). Over drusen, RPE morphology transitioned smoothly from the age-normal layer toward the top, suggesting transdifferentiation. The sub-RPE-basal lamina space had RPE-derived cells (n = 87) and non-RPE phagocytes (n = 49), including macrophages and giant cells. CONCLUSION: Numerous sub-RPE-basal lamina cells of several types are consistent with the documented presence of proinflammatory lipids in drusen and aged Bruch's membrane. The relatively compartmentalized abundance of infiltrating cells suggests that drusen contents are more inflammatory than subretinal drusenoid deposit, perhaps reflecting their environments. Ectopic RPE occurs frequently. Some manifest as hyperreflective foci. More cells may be visible as optical coherence tomography technologies evolve.

MULTIZONAL OUTER RETINOPATHY AND RETINAL PIGMENT EPITHELIOPATHY (MORR): A Newly Recognized Entity or an Unusual Variant of AZOOR?

PURPOSE: To describe specific clinical, multimodal imaging, and natural history features of an unusual variant of acute zonal occult outer retinopathy. METHODS: Retrospective, observational, longitudinal, multicenter case series. Patients exhibiting this unusual clinical condition among cases previously diagnosed with acute zonal occult outer retinopathy were included. Multimodal imaging, laboratory evaluations, and genetic testing for inherited retinal diseases were reviewed. RESULTS: Twenty eyes from 10 patients (8 females and 2 males) with a mean age of 54.1 ± 13.3 years (range, 38-71 years) were included. The mean follow-up duration was 13.1 ± 5.3 years (range, 8-23 years). Presenting symptoms were bilateral in 7 patients (85% of eyes) and included scotomata and photopsia. All patients had bilateral lesions at presentation involving the peripapillary and far peripheral retina. Baseline optical coherence tomography showed alteration of the retinal pigment epithelium and photoreceptor layers corresponding to zonal areas of fundus autofluorescence abnormalities. Centrifugal and centripetal progression of the peripapillary and far-peripheral lesions, respectively, occurred over the follow-up, resulting in areas of complete outer retinal and retinal pigment epithelium atrophy. CONCLUSION: Initial alteration of photoreceptors and retinal pigment epithelium and a stereotypical natural course that includes involvement of the far retinal periphery, characterize this unusual condition. It may represent a variant of acute zonal occult outer retinopathy or may be a new entity. We suggest to call it multizonal outer retinopathy and retinal pigment epitheliopathy .

STELLATE MULTIFORM AMELANOTIC CHOROIDOPATHY: Clinical and Multimodal Imaging Features.

PURPOSE: To describe the clinical and multimodal imaging features of stellate multiform amelanotic choroidopathy (SMACH; also known as serous maculopathy due to aspecific choroidopathy). METHODS: Retrospective observational case series of eyes presenting with SMACH. Multimodal imaging including fundus photography, optical coherence tomography (OCT), OCT angiography (OCTA), and indocyanine green angiography (ICGA) was analyzed. RESULTS: Eighteen eyes from 18 patients (mean age: 28 ± 19 years) were included. The mean follow-up duration was 9 years. Ophthalmoscopy showed a yellowish orange, dendriform choroidal lesion. At presentation, subretinal fluid (SRF) was seen in 10 of 18 cases (56%). Eight patients (44%) showed no evidence of SRF during a mean follow-up of 6 years. Cross-sectional OCT showed hyperreflective fibrous-like changes within the inner choroid with choriocapillaris flow preservation on OCTA. En face OCT showed a hyperreflective choroidal lesion with finger-like projections oriented in a stellate configuration. On ICGA, SMACH showed early and late hypofluorescence. None of the cases showed lesion growth. CONCLUSION: SMACH seems to be a unilateral choroidopathy characterized by distinctive multimodal imaging features. As SRF was absent in some cases, while a dendriform pattern was a consistent finding in all eyes, the authors propose renaming this entity "stellate multiform amelanotic choroidopathy," a name that retains its previous abbreviation "SMACH."

THE CHRYSANTHEMUM PHENOTYPE OF IDIOPATHIC MULTIFOCAL CHOROIDITIS.

PURPOSE: To describe the clinical characteristics and multimodal imaging features of a distinctive subtype of active idiopathic multifocal choroiditis (iMFC) lesions with grey-yellow chorioretinal lesions surrounded by smaller satellite dots, a presentation referred to as "chrysanthemum lesions." METHODS: Retrospective, observational, multicenter case series of eyes with active iMFC and chrysanthemum lesions. Multimodal imaging features were reviewed and presented. RESULTS: Twenty-five eyes from 20 patients (12 women and 8 men), with a mean age of 35.8 ± 17.0 years (range, 7-78 years) were included. Chrysanthemum lesions were equally located in the macula (48.0%) or the mid/far periphery (52.0%). The number of lesions per eye varied from 1 (16.0%) to more than 20 (56.0%). On optical coherence tomography, chrysanthemum lesions showed typical features of iMFC, including subretinal hyperreflective material splitting the retinal pigment epithelium/Bruch membrane. Chrysanthemum lesions were hypoautofluorescent on fundus autofluorescence imaging, hyperfluorescent on fluorescein angiography, hypofluorescent on indocyanine green angiography, and associated with choriocapillaris flow signal deficit on optical coherence tomography angiography. CONCLUSION: Active iMFC may present with findings resembling chrysanthemum lesions. The distinctive lesion morphology on ophthalmoscopic examination, the large number of lesions, and the high prevalence of exclusive midperipheral and far peripheral involvement may represent a distinctive phenotype of iMFC.

ARE THERE TWO FORMS OF MULTIPLE EVANESCENT WHITE DOT SYNDROME?

PURPOSE: To analyze the nature of multiple evanescent white dot syndrome (MEWDS) and differentiate an idiopathic or primary form of MEWDS from a secondary form that is seen in association with other clinical conditions affecting the posterior segment of the eye. METHODS: Clinical and multimodal imaging findings including color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography of patients with secondary MEWDS are presented. RESULTS: Twenty consecutive patients with secondary MEWDS were evaluated. Fifteen patients were female. Most were young adults aged between 20 to 40 years with myopia (less than -6 diopters). Pathologic conditions associated with the secondary MEWDS reaction were high myopia (greater than -6 diopters) in two eyes, previous vitreoretinal surgery for rhegmatogenous retinal detachment in 2 eyes, and manifestations of multifocal choroiditis in 18 eyes. In all eyes, the MEWDS lesions followed a course of progression and resolution independent from the underlying condition. CONCLUSION: Secondary MEWDS seems to be an epiphenomenon ("EpiMEWDS") that may be seen in association with clinical manifestations disruptive to the choriocapillaris-Bruch membrane-retinal pigment epithelium complex.

PUNCTATE INNER CHOROIDOPATHY-LIKE REACTIONS IN UNRELATED RETINAL DISEASES.

PURPOSE: To report a cohort of patients with a punctate inner choroidopathy (PIC)-like reaction in concurrent, unrelated, chorioretinal disorders. METHODS: This was a retrospective observational study of patients seen at two referral centers with lesions consistent with PIC on multimodal imaging; patients with lesions resembling idiopathic multifocal choroiditis were also included. Active PIC-like lesions appeared as focal hyperreflective lesions splitting the retinal pigment epithelium/Bruch membrane (RPE/BrM) complex on optical coherence tomography. Chronic PIC-like lesions included subretinal fibrosis, multifocal punched-out chorioretinal atrophy, and curvilinear streaks. Patients' demographics, additional imaging features, and treatment responses were collected and summarized. RESULTS: Twenty-two eyes of 16 patients with a PIC-like reaction were included (75% females; median age 40 years). Underlying diagnoses included hereditary retinal conditions (10 patients, 63%) and acquired etiologies, all characterized by the RPE/BrM or outer retinal disruption. Fifteen eyes (68%) had active PIC-like lesions; seven eyes (32%) had chronic PIC-like lesions. Active PIC-like lesions regressed with time and responded to systemic steroids. Subretinal fibrosis (3 eyes, 20%), macular atrophy (3 eyes, 20%), and concomitant subretinal fibrosis and macular atrophy (5 eyes, 33%) developed on follow-up. Recurrences occurred in five eyes (23%). CONCLUSION: RPE/BrM or outer retina disruption may trigger a PIC-like reaction in susceptible patients, presumably because of the loss of immune privilege. A PIC-like reaction may influence the clinical progression and the visual prognosis of the primary chorioretinal disease.

ULTRAWIDEFIELD PSEUDOCOLOR RETINAL IMAGING VERSUS REAL-COLOR FUNDUS PHOTOGRAPHY FOR DETECTION OF INTRARETINAL PIGMENT MIGRATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare pseudocolor Optos ultrawidefield (UWF) retinal images with conventional real-color fundus photography (CFP) for detecting macular hyperpigmentary changes in intermediate age-related macular degeneration. METHODS: This retrospective study included 50 patients diagnosed with intermediate age-related macular degeneration. All patients underwent Optos imaging and CFP. The overall accuracy to visualize hyperpigmentation and its morphologic features was graded by two independent readers using a standardized grid. Structural and en face optical coherence tomography images were correlated with UWF and CFP images to determine spatial correspondence of pigment clumping on fundus images and hyperreflective foci on optical coherence tomography. RESULTS: One hundred eyes of 50 patients had hyperpigmentary changes on funduscopic examination and were included. The intragraders and intergraders agreements were high for all measurements (P < 0.001). At least one hyperpigmentary changes within the standardized grid was detected in 93% using CFP and 100% using UWF camera (P = 0.02). The total area of hyperpigmentation measured on UWF images was significantly higher than on CFP images (P < 0.001). There was a significant correlation between the presence of hyperpigmentary changes on both CFP and UWF images and hyperreflective foci on structural optical coherence tomography (P < 0.001). CONCLUSION: Ultrawidefield fundus images allow high detection and accurate quantification of macular hyperpigmentary changes in intermediate age-related macular degeneration compared with conventional CFP.

BACILLARY LAYER DETACHMENT: MULTIMODAL IMAGING AND HISTOLOGIC EVIDENCE OF A NOVEL OPTICAL COHERENCE TOMOGRAPHY TERMINOLOGY: Literature Review and Proposed Theory.

PURPOSE: To clarify the histologic basis of bacillary layer detachment (BALAD) through a review of the current literature and an analysis of retinal imaging. METHODS: The literature for previous reports of BALAD were reviewed. An analysis of retinal images was performed to support anatomical conclusions. RESULTS: A total of 164 unique patients with BALAD on optical coherence tomography (OCT) were identified from the published literature. Twenty-two underlying etiologies, all associated with subretinal exudation, were identified. Forty-one different OCT terminologies were found. The defining OCT feature of BALAD was a split at the level of the photoreceptor inner segment myoid creating a distinctive intraretinal cavity. Resolution of BALAD was followed by a rapid restoration of the ellipsoid zone. Histology of age-related macular degeneration eyes suggests that individual photoreceptors can shed inner segments. Furthermore, detachment of the entire layer of inner segments is a common postmortem artifact. It is proposed that BALAD occurs when outwardly directed forces promoting attachment of photoreceptor outer segments to the retinal pigment epithelium exceed the tensile strength of the photoreceptor inner segment myoid. CONCLUSION: This review serves to strengthen the OCT nomenclature "bacillary layer detachment," based on specific reflectance information obtained by OCT and previously published histologic observations.

Focal Scleral Nodule: A New Name for Solitary Idiopathic Choroiditis and Unifocal Helioid Choroiditis.

PURPOSE: To evaluate multimodal imaging findings of solitary idiopathic choroiditis (SIC; also known as unifocal helioid choroiditis) to clarify its origin, anatomic location, and natural course. DESIGN: Multicenter retrospective observational case series. PARTICIPANTS: Sixty-three patients with SIC in 1 eye. METHODS: Demographic and clinical data were collected. Multimodal imaging included color fundus photography, OCT (including swept-source OCT), OCT angiography (OCTA), fundus autofluorescence, fluorescein and indocyanine green angiography, and B-scan ultrasonography. MAIN OUTCOME MEASURES: Standardized grading of imaging features. RESULTS: Mean age at presentation was 56 ± 15 years (range, 12-83 years). Mean follow-up duration in 39 patients was 39 ± 55 months (range, 1 month-25 years). The lesions measured a mean of 2.4 × 2.1 mm in basal diameter, were located inferior (64%) or nasal to the optic disc, and appeared yellow (53%). No systemic associations were found. The lesions all appeared as an elevated subretinal mass, with OCT demonstrating all lesions to be confined to the sclera, not the choroid. On OCT, the deep lesion margin was visible in 12 eyes with a mean lesion thickness of 0.6 mm. Overlying choroidal thinning or absence was seen in 95% (mean choroidal thickness, 28 ± 35 µm). Mild subretinal fluid was observed overlying the lesions in 9 patients (14%). Retinal pigment epithelial disruption and overlying retinal thinning was observed in 56% and 57%, respectively. OCT angiography was performed in 13 eyes and demonstrated associated choroidal and lesional flow voids. Four lesions (6%) were identified at the macula, leading to visual loss in 1 patient. One lesion demonstrated growth and another lesion showed spontaneous resolution. CONCLUSIONS: In this largest series to date, multimodal imaging of SIC demonstrated a scleral location in all patients. The yellow and white clinical appearance may be related to scleral unmasking resulting from atrophy of overlying tissues. Additional associated features included documentation of deep margin on swept-source OCT, trace subretinal fluid in a few patients, and OCTA evidence of lesional flow voids. Because of the scleral location of this lesion in every patient, a new name, focal scleral nodule, is proposed.

Inverted internal limiting membrane flap technique versus complete internal limiting membrane peeling in large macular hole surgery: a comparative study.

BACKGROUND: To compare the anatomical and functional outcomes of the inverted internal limiting membrane (ILM) flap technique and the complete ILM removal in the treatment of large stage 4 macular hole (MH) > 400 µm and to evaluate reconstructive anatomical changes in foveal microstructure using spectral-domain optical coherence tomography. METHODS: This is a retrospective, consecutive, nonrandomized comparative study of patients affected by idiopathic, myopic or traumatic stage 4 MH (minimum diameter > 400 µm) treated with 25-gauge pars-plana vitrectomy with either complete ILM peeling (n = 23, Group 1) or inverted ILM flap technique (n = 23, Group 2), between August 2016 and August 2018. Main outcomes measured were the MH closure rate assessed by spectral-domain optical coherence tomography and the best-corrected visual acuity (BCVA) at six months. Foveal microstructure reconstructive changes were evaluated using SD-OCT to determine predictive factors of postoperative BCVA. RESULTS: Closure of MH was achieved in 16/23 cases of Group 1 (70%) and in 22/23 cases of the Group 2 (96%). Surgical failure was reported in 6 cases of Group 1 and 1 case of Group 2. The MH closure rate was significantly higher with the inverted ILM flap technique (P-value = 0.02). Average BCVA (LogMAR) changed from 1.04 ± 0.32 to 0.70 ± 0.31 in Group 1 and from 0.98 ± 0.22 to 0.45 ± 0.25 in Group 2 (P-value = 0.005) at 6 months. Improvement in BCVA (> 0.3 LogMAR units) was statistically higher in the Group 2 (P-value = 0.03). Restoration of foveal microstructure was significantly higher in the Group 2 at 6 months (52% vs 9%, P-value < 0.01). In Group 2, the integrity of the external limiting membrane at 3 months postoperatively was the only significant feature correlated with postoperative BCVA at 6 months (r = 0.562; P-Value = 0.01, forward stepwise regression analysis). CONCLUSION: Inverted ILM flap technique is more effective than the classic ILM peeling for the closure of large stage 4 MHs > 400 µm, improving both anatomical and functional outcomes. Early recovery of the external limiting membrane at 3 months is a positive predictive value of postoperative BCVA 6 months after inverted ILM flap technique.

Pigmented paravenous retinochoroidal atrophy associated with Vogt-Koyanagi-Harada disease: a case report.

BACKGROUND: To describe a unique case of pigmented paravenous retinochoroidal atrophy that developed several years after Vogt-Koyanagi-Harada disease. CASE PRESENTATION: A 28-year-old woman presented with gradual vision loss in both eyes and nyctalopia for 2 years. Past medical history was relevant for Vogt-Koyanagi-Harada disease since the age of 19 and positive HLA-DR4. Funduscopic examination revealed perivascular pigmentary clumping and atrophic changes radiating from the optic disks. Spectral domain optical coherence tomography through the macula demonstrated perifoveal outer retinal layers loss with cystic degeneration. Fundus autofluorescence showed zonal areas of hypoautofluorescence corresponding to the areas of atrophy. Full-field electroretinogram identified mildly reduced scotopic and photopic responses. The patient was diagnosed with pigmented paravenous retinochoroidal atrophy. CONCLUSIONS: Pigmented paravenous retinochoroidal atrophy may be acquired after Vogt-Koyanagi-Harada disease. Pathogenesis of pigmented paravenous retinochoroidal atrophy may involve inflammatory-related precursors on a background of genetic predisposition.

Decompression retinopathy following nonpenetrating deep sclerectomy for primary congenital glaucoma.

BACKGROUND: To describe a unique case of decompression retinopathy manifesting as pre-macular subhyaloid hemorrhage that occurs in a nine-day old child after undergoing a non-penetrating deep sclerectomy for primary congenital glaucoma. CASE PRESENTATION: We report a single case of a 9-day-old boy who was referred to our department of ophthalmology for bilateral buphtalmia and corneal edema. He presented marked elevation of the intraocular pressure in both eyes (22 mmHg and 26 mmHg, in the right eye and left eye respectively) associated with significant optic nerve cupping. Non-penetrating deep sclerectomy was performed for each eye, with effective reduction of the intraocular pressure during the first week postoperatively (11 mmHg and 7 mmHg in the right eye and left eye respectively). The right eye presented an isolated subhyaloid hemorrhage located in the pre-macular area, persisting 3 weeks after the initial surgery and requiring pars-plana vitrectomy to clear the visual axis. This uncommon complication was identified as decompression retinopathy. The intraocular pressure remained controlled in the normal range three years after initial surgery in both eyes, with reversal of optic disc cupping. CONCLUSIONS: Decompression retinopathy is a potential complication after non-penetrating deep sclerectomy in primary congenital glaucoma, requiring prompt treatment strategy to prevent potential organic amblyopia.