Concurrent ciliary body detachment in patients presenting with serous choroidal detachment following glaucoma surgery.

PURPOSE: To examine the rate of ciliary body detachment in patients with choroidal detachment following glaucoma surgery and its effect on the clinical course, management, and prognosis. METHODS: A prospective observational case-series study. Patients with choroidal detachment following glaucoma surgery in 2018-2019 were included. All underwent complete ophthalmological examination and ultrasound biomicroscopy for evaluation of the presence and extent of ciliary body detachment. Follow-up examinations including ultrasound biomicroscopy scans were performed at 1 week, 1 month, 3 months, and 6 months. RESULTS: Eight patients (8 eyes) were enrolled, 4 male and 4 female, of mean age 72 years (range 60-83). Five patients underwent trabeculectomy with mitomycin C (0.02%), which was combined with phacoemulsification cataract extraction in one; two underwent Ahmed glaucoma valve implantations, and one underwent ab-interno Xen45 gel stent implantation with mitomycin C (0.02%). The mean intraocular pressure was 26.0 ± 7.65 mmHg preoperatively, dropping to 6.9 ± 2.64 mmHg on first postoperative day one. Mean time from surgery to diagnosis of choroidal detachment was 11.6 ± 5.73 days. Ciliary body detachment was identified by ultrasound biomicroscopy in all patients, ranging between one and four quadrants. All patients were treated with topical steroids and cycloplegics; three (37.5%) received oral steroids. No surgical intervention for the choroidal or ciliary body detachments was indicated. CONCLUSIONS: In this real-world prospective study, concurrent ciliary body detachment was identified in all patients who presented with choroidal detachment following glaucoma surgery. This observation may deepen our understanding of the mechanism underlying the hypotony that is often seen after glaucoma surgery.

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.

Outcomes of Combined Phacovitrectomy Without Corneal Suturing.

BACKGROUND: During combined phacovitrectomy, it is common practice to suture the main corneal incision to prevent intraoperative and postoperative wound leak. However, it may be possible to avoid suturing using a self-sealing corneal incision technique as in standard cataract surgery. OBJECTIVES: To evaluate the clinical outcome, safety, and complications of combined phacovitrectomy without preventive suturing. METHODS: This retrospective case series study included consecutive patients who underwent combined phacovitrectomy between January 2018 and June 2019 for mixed indications. Surgeries were performed at a tertiary university hospital. All surgeries were performed by the same two retinal surgeons. Cataract surgery was performed first, followed by insertion of trocars and vitrectomy. Corneal sutures were not planned but were used at the discretion of the surgeon. RESULTS: The cohort included 106 eyes of 102 patients. Suturing of the main corneal incision was deemed necessary in five cases (5%) because of a main incision leak or anterior chamber shallowing during trocar insertion. No other complications related to the absence of prophylactic corneal sutures were encountered during surgery or follow-up. CONCLUSIONS: Preventive corneal suturing may not be necessary in combined phacovitrectomy surgery and can be used in the few cases in which it is indicated during surgery.

Intravitreal Tissue Plasminogen Activator Injection for the Treatment of Proliferative Vitreoretinopathy in a Rabbit Model.

INTRODUCTION: The purpose of this study is to evaluate the effect of intravitreal injection of tissue plasminogen activator (tPA) on proliferative vitreoretinopathy (PVR). METHODS: PVR was induced in a rabbit model by intraocular injection of dispase (0.05 U/0.1 mL). Progression of PVR was followed by indirect ophthalmic examination. Following 6 weeks, five animals received intravitreal injection of 25 µg/0.1 mL tPA and four were injected with balanced salt solution (BSS). Animals were euthanized at 48 hours following tPA/BSS injection and eyes were enucleated for histological evaluation and staining with α-smooth muscle actin (αSMA) and Sirius Red. RESULTS: Following tPA injection, one eye had a reduction in PVR from grade 2 to 1 and three eyes remained stable. Following BSS, PVR grade was unchanged in three eyes. In one eye in each group, the severity of PVR couldn't be assessed due to limited view. Staining with αSMA showed reduced presence of fibroblasts in eyes injected with tPA compared with those injected with BSS. Collagen type I and III, demonstrated by Sirius Red staining, was reduced in the tPA group in comparison to controls. CONCLUSION: Our results suggest that intravitreally injected tPA may show an inhibitory effect on PVR progression. Further exploration in clinical trials is desired.

FULL-THICKNESS MACULAR HOLE IN AGE-RELATED MACULAR DEGENERATION PATIENTS WITH TWO DISTINCT ENTITIES: A Multicenter Study.

PURPOSE: To describe optical coherence tomography characteristics of full-thickness macular holes (FTMHs) in age-related macular degeneration patients. METHODS: A multicenter, retrospective, observational case series of patients diagnosed with age-related macular degeneration and FTMHs seen between January 1, 2009, and January 3, 2020. Clinical charts and spectral-domain optical coherence tomography images were reviewed. Optical coherence tomography findings included FTMH-inverted trapezoid or hourglass appearance, central macular thickness (CMT), complete retinal pigment epithelium and complete retinal outer retinal atrophy, and presence of pigment epithelium detachment and epiretinal membrane. The mean outcome was the morphologic and functional characterization of different subtypes of FTMHs. RESULTS: A total of 86 eyes of 85 consecutive patients, with mean age of 80.31 ± 8.06 and mean best-corrected visual acuity of 1.17 ± 0.58 logarithm of the minimal angle of resolution. Two different subtypes of FTMHs were identified: tractional and degenerative. Fifty (58%) degenerative FTMHs characterized with inverted trapezoid appearance and 36 (42%) tractional FTMHs characterized with hourglass appearance. Degenerative FTMHs presented with 66% of CMT < 240 µm, 14% of CMT > 320, and 70% of complete retinal outer retinal atrophy, in comparison with 41% of CMT < 240 µm, 42.9% of CMT > 320%, and 20% of complete retinal outer retinal atrophy in the tractional FTMH group (P = 0.002, 0.003, <0.001, respectively). The presence of epiretinal membrane and pigment epithelium detachment where significantly higher in tractional FTMHs (P = 0.02, 0.03, respectively). CONCLUSION: Degenerative and tractional FTMHs may be two distinct clinical entities. Discerning degenerative from tractional FTMHs is possible by using optical coherence tomography features including shape of the FTMHs, CMT, internal-external ratio of FTMHs, and presence of complete retinal outer retinal atrophy, pigment epithelium detachment, and epiretinal membrane.

Ocular Trauma Caused by Confetti Cannons.

BACKGROUND: Eye trauma is an unfortunate and often preventable cause of vision loss. Confetti cannons are common causes of injury. Awareness of ocular hazards of confetti cannons remains low because of limited reports describing ophthalmic injuries following their use. OBJECTIVES: To describe outcomes of ocular trauma caused by confetti cannons and to increase recognition of their ocular risks. METHODS: A retrospective analysis was conducted of eye injuries caused by confetti cannons presenting to a single medical center between 2016 and 2020. Data collected included age, gender, eye injured, ocular damage, visual outcome, and details of surgeries performed. RESULTS: Overall, six consecutive patients (2 males, mean age 19.5 ± 9.74 years) were identified and studied. In all patients only one eye was injured (3 right eyes) during a private celebration, most commonly (n=5) to a bystander while in the vicinity of a cannon operated by someone else. Most common eye injuries included corneal erosion (n=4), traumatic hyphema (n=4), and retinal edema (n=3). Mean initial logMAR visual acuity in the injured eye was 0.73 ± 0.18, improving to 0.25 ± 0.16 at the final visit (P = 0.125). Two patients underwent eye surgery due to their trauma: one to repair globe penetration and another to undergo intravitreal injection of tissue plasminogen activator and C3F8 for submacular hemorrhage, followed 8 months later by intravitreal bevacizumab injection for choroidal neovascularization. CONCLUSIONS: Confetti cannons pose hazards that can cause severe ocular trauma resulting in permanent vision loss. Increasing awareness of device hazards is necessary to prevent eye injuries.

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.

PATIENTS WEARING FACE MASKS DURING INTRAVITREAL INJECTIONS MAY BE AT A HIGHER RISK OF ENDOPHTHALMITIS.

PURPOSE: To investigate the safety of face masks worn by patients during intravitreal injections. METHODS: A prospective, qualitative, interventional study performed in a tertiary university hospital. Healthy volunteers were asked to wear three different professional surgical face masks while air leaks around the eyes were monitored. Three types of masks were investigated as follows: 1) surgical face mask with four tying strips, 2) surgical face mask with elastic ear loops and 3) 2200 N95 tuberculosis particulate face mask. For each session the periocular area was inspected for air leak during normal respiration, speech, and deep respiration. Detection of air leak was performed using the following two professional thermal cameras: FLIR A310-thermal camera and EyeCGas 2.0-super sensitive infrared camera used for detection of minute fugitive emissions of industrial gases. RESULTS: Ten healthy volunteers were enrolled in this study. The experiment was repeated 45 times for each camera; 3 times for each of 3 mask types, on 5 volunteers, for a total of 90 trials. Air jets were detected originating from the superior edges of the masks radiating toward the eyes in 81% (73/90) of cases in total; 71% (32/45) with the FLIR camera and 91% (41/45) with the OPGAL camera. Air leaks were detected with all investigated mask types. CONCLUSION: Patients wearing face masks during intravitreal injections may be at a higher risk of endophthalmitis. Until further data are available, we recommend verifying proper face mask fitting and either taping the upper edges of the face masks with a medical adhesive tape or using an adhesive surgical drape around the injected eye.

CUTICULAR DRUSEN: Risk of Geographic Atrophy and Macular Neovascularization.

PURPOSE: Cuticular drusen (CD) have been associated with manifestations of age-related macular degeneration such as atrophy and neovascularization in the macula. In this study, eyes with CD were followed and investigated for the estimated 5-year risk of progression to sequelae of age-related macular degeneration such as geographic atrophy (GA) and macular neovascularization (MNV). METHODS: A consecutive series of patients with CD were followed for the development of GA and MNV. Whenever possible, they were also studied retrospectively. The patients with CD were categorized into three phenotypic groups. Phenotype 1: eyes had concentrated, densely populated CD in the macular and paramacular area, Phenotype 2: eyes showed scattered CD in the posterior fundus, and Phenotype 3: involved eyes with CD mixed with large drusen (>200 µm). The 5-year incidence of progression was then estimated using a Kaplan-Meier estimator. RESULTS: A total of 63 eyes from 38 patients (35 women with a mean age at presentation of 58.9 ± 14.2 years) were studied and followed for a mean of 40 ± 18 months. Thirteen patients had single eyes with GA (84.5%; 11/13) or MNV (15.5%; 2/13) in one eye at presentation and were subsequently excluded. Geographic atrophy developed in 19.0% (12/63) of eyes and MNV in 4.8% (3/63) of eyes. The cumulative estimated 5-year risk of GA and MNV was 28.4% and 8.7%, respectively. The estimated 5-year incidence of MNV or GA was 12.6%, 50.0%, and 51.6% in Phenotype 1, Phenotype 2, and Phenotype 3, respectively (P = 0.0015, log-rank test). No difference in risk was found in the development of GA or MNV (P = 0.11) between the subgroup of patients presenting with GA or MNV in their fellow eye and those with both eyes included. CONCLUSION: When patients with CD are followed longitudinally, there was a significant risk of progression to GA or MNV for Phenotype 2 and Phenotype 3. Patients with CD are commonly first diagnosed in the fifth decade of life, and there is a female predominance. Clinicians should use multimodal imaging to detect and be aware of the risk of progression to manifestations of GA and MNV. These risks of GA and MNV suggest that patients with CD may be part of the overall spectrum of age-related macular degeneration.

In vivo imaging of the fibrillar architecture of the posterior vitreous and its relationship to the premacular bursa, Cloquet's canal, prevascular vitreous fissures, and cisterns.

PURPOSE: To describe the fibrillar architecture of the posterior cortical vitreous and identify variations across eyes of different axial lengths in vivo. METHODS: Sixty-four eyes of 32 subjects were examined with swept-source optical coherence tomography (SS-OCT). Grading of vitreous degeneration, presence of vitreous cisterns/lacunae, posterior hyaloid status, directionality of vitreous fibers and their relations to vitreous spaces, and lamellar reflectivity of the posterior vitreous were assessed. RESULTS: A consistent pattern of fibrillar organization was discovered. Eyewall parallel fibers formed a dense meshwork over the retinal surface and fibers oriented in a perpendicular fashion to this meshwork were found to envelop the various vitreous spaces, intersecting at variable angles of insertion to the eyewall parallel fibers. Lamellar reflectivity suggestive of splitting of the cortical fibrillar meshwork was detected in 27 eyes (42%) with 56% of these eyes demonstrating perpendicularly oriented intersecting fibers. Fifty-six percent of eyes with lamellar reflectivity had an axial length > 25 mm. CONCLUSION: SS-OCT imaging revealed fibrillar organization of the posterior vitreous. Eye wall parallel hyperreflectivity of cortical vitreous was a universal finding. This pattern is suggestive of a splitting of cortical vitreous tissue and may represent a precursor to vitreoschisis. Perpendicular fibers appear to be important constituents of the walls of the various liquid vitreous spaces.

Comparison of Subconjunctival Aflibercept and Betamethasone for the Treatment of Formed Corneal Neovascularization in a Rabbit Model.

AIM: To compare the efficacy of aflibercept (Eylea®), a potent antivascular endothelial growth factor (VEGF) agent, with betamethasone (Celestone®) and placebo for the treatment of formed corneal neovascularization in a rabbit model. METHODS: A central corneal chemical burn was created in the right eye of 24 New Zealand albino rabbits. Four weeks later, the rabbits were randomly divided into 4 equal groups for subconjunctival injection of aflibercept, betamethasone, aflibercept+ betamethasone, or saline (control). Digital photographs taken at weekly intervals were rated by 2 masked observers for extent, centricity, and density of corneal neovascularization according to a predefined scale. The percentage of corneal surface involved by neovascularization was quantified by image analysis software (Fiji-J). The change in corneal neovascularization from treatment administration (4 weeks after injury) to 4 weeks later (8 weeks after injury) was assessed. The rabbits were then euthanized, and their eyes were enucleated and processed for histopathological and immunofluorescence studies. RESULTS: There was no significant difference in the change in corneal neovascularization after treatment among the 4 groups according to the digital images (p > 0.15) or histological evaluation with hematoxylin and eosin (p > 0.08). On immunofluorescence assay, a lower VEGF concentration was observed in all treatment groups compared to the control group. CONCLUSIONS: In this rabbit model, corneal neovascularization induced by chemical burn failed to regress with treatment with aflibercept, betamethasone, or their combination.

Choroidal and Sub-Retinal Pigment Epithelium Caverns: Multimodal Imaging and Correspondence with Friedman Lipid Globules.

PURPOSE: To survey Friedman lipid globules by high-resolution histologic examination and to compare with multimodal imaging of hyporeflective caverns in eyes with geographic atrophy (GA) secondary to age-related macular (AMD) and other retinal diseases. DESIGN: Histologic survey of donor eyes with and without AMD. Clinical case series with multimodal imaging analysis. PARTICIPANTS: Donor eyes (n = 139; 26 with early AMD, 13 with GA, 40 with nAMD, 52 with a healthy macula, and 8 with other or unknown characteristics) and 41 eyes of 28 participants with GA (n = 16), nAMD (n = 8), Stargardt disease (n = 4), cone dystrophy (n = 2), pachychoroid spectrum (n = 6), choroidal hemangioma (n = 1), and healthy eyes (n = 4). METHODS: Donor eyes were prepared for macula-wide epoxy resin sections through the foveal and perifoveal area. In patients, caverns were identified as nonreflective spaces on OCT images. Multimodal imaging included color and red-free fundus photography; fundus autofluorescence; fluorescein and, indocyanine green angiography; OCT angiography; near-infrared reflectance; and confocal multispectral (MultiColor [Spectralis, Heidelberg Engineering, Germany]) imaging. MAIN OUTCOME MEASURES: Presence and morphologic features of globules, and presence and appearance of caverns on multimodal imaging. RESULTS: Globules were found primarily in the inner choroidal stroma (91.0%), but also localized to the sclera (4.9%) and neovascular membranes (2.1%). Mean diameters of solitary and multilobular globules were 58.9±37.8 µm and 65.4±27.9 µm, respectively. Globules showed morphologic signs of dynamism including pitting, dispersion, disintegration, and crystal formation. Evidence for inflammation in the surrounding tissue was absent. En face OCT rendered sharply delimited hyporeflective areas as large as choroidal vessels, frequently grouped around choroid vessels or in the neovascular tissue. Cross-sectional OCT revealed a characteristic posterior hypertransmission. OCT angiography showed absence of flow signal within caverns. CONCLUSIONS: Based on prior literature documenting OCT signatures of tissue lipid in atheroma and nAMD, we speculate that caverns are lipid rich. Globules, with similar sizes and tissue locations in AMD and healthy persons, are candidates for histologic correlates of caverns. The role of globules in chorioretinal physiologic features, perhaps as a lipid depot for photoreceptor metabolism, is approachable through clinical imaging.

Cuticular Drusen: Clinical Phenotypes and Natural History Defined Using Multimodal Imaging.

PURPOSE: To define the range and life cycles of cuticular drusen phenotypes using multimodal imaging and to review the histologic characteristics of cuticular drusen. DESIGN: Retrospective, observational cohort study and experimental laboratory study. PARTICIPANTS: Two hundred forty eyes of 120 clinic patients with a cuticular drusen phenotype and 4 human donor eyes with cuticular drusen (n = 2), soft drusen (n = 1), and hard drusen (n = 1). METHODS: We performed a retrospective review of clinical and multimodal imaging data of patients with a cuticular drusen phenotype. Patients had undergone imaging with various combinations of color photography, fluorescein angiography, indocyanine green angiography, near-infrared reflectance, fundus autofluorescence, high-resolution OCT, and ultrawide-field imaging. Human donor eyes underwent processing for high-resolution light and electron microscopy. MAIN OUTCOME MEASURES: Appearance of cuticular drusen in multimodal imaging and the topography of a cuticular drusen distribution; age-dependent variations in cuticular drusen phenotypes, including the occurrence of retinal pigment epithelium (RPE) abnormalities, choroidal neovascularization, acquired vitelliform lesions (AVLs), and geographic atrophy (GA); and ultrastructural and staining characteristics of druse subtypes. RESULTS: The mean age of patients at the first visit was 57.9±13.4 years. Drusen and RPE changes were seen in the peripheral retina, anterior to the vortex veins, in 21.8% of eyes. Of eyes with more than 5 years of follow-up, cuticular drusen disappeared from view in 58.3% of eyes, drusen coalescence was seen in 70.8% of eyes, and new RPE pigmentary changes developed in 56.2% of eyes. Retinal pigment epithelium abnormalities, AVLs, neovascularization, and GA occurred at a frequency of 47.5%, 24.2%, 12.5%, and 25%, respectively, and were significantly more common in patients older than 60 years of age (all P < 0.015). Occurrence of GA and neovascularization were important determinants of final visual acuity in eyes with the cuticular drusen phenotype (both P < 0.015). Small cuticular drusen typically demonstrated a homogenous ultrastructural appearance similar to hard drusen, whereas fragmentation of the central and basal contents was seen frequently in larger cuticular drusen. CONCLUSIONS: Although the ultrastructural characteristics of cuticular drusen appear more similar to those of hard drusen, their lifecycle and macular complications are more comparable with those of soft drusen. Cuticular drusen phenotype may confer a unique risk for the development of GA and neovascularization.

INNER CHOROIDAL FLOW SIGNAL ATTENUATION IN PACHYCHOROID DISEASE: Optical Coherence Tomography Angiography.

PURPOSE: To study zones of reduced inner choroidal flow signal, foci of reduced inner choroidal thickness, and pathologically dilated Haller layer vessels (pachyvessels) in eyes with pachychoroid disease using optical coherence tomography (OCT) and OCT angiography. METHODS: Patients with treatment-naive pachychoroid disease were recruited. All patients prospectively underwent swept-source OCT and OCT angiography. Zones of reduced choriocapillaris flow were labeled and enumerated. Areas where reduced flow signal was attributable to masking/artifacts were excluded. Regions of inner choroidal thinning were identified on structural OCT and labeled. Overlap between reduced choriocapillaris flow and structural inner choroidal attenuation was quantified using Jaccard indices. The relationship of reduced flow to pachyvessels was recorded. RESULTS: Twenty-four eyes of 19 patients were identified. All eyes exhibited at least one zone of reduced flow. A total of 146 flow signal attenuation zones were identified. Sixty-two (42%) of 146 zones showed overlap or proximity with structural inner choroidal thinning. The mean Jaccard index per eye was 0.10 (SD = 0.08). Pachyvessels were spatially related to 100 (68%) of 146 zones of flow attenuation. CONCLUSION: Zones of reduced choriocapillaris flow are prevalent in eyes with pachychoroid disease. Approximately 60% of these zones anatomically correlate with pachyvessels. Inner choroidal ischemia seems related to the pathogenesis of pachychoroid diseases.

REDUCED CHORIOCAPILLARIS FLOW IN EYES WITH TYPE 3 NEOVASCULARIZATION AND AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To study choriocapillaris (CC) flow in eyes with Type 3 neovascularization (NV) and age-related macular degeneration, using optical coherence tomography angiography analysis. METHODS: In this multicenter, retrospective, observational study, we collected data from 21 patients with unilateral Type 3 NV and age-related macular degeneration, based on clinical examination, structural optical coherence tomography, and fluorescein angiography when available. An additional group of 20 nonneovascular age-related macular degeneration eyes with unilateral Type 1 or Type 2 NV due to age-related macular degeneration was included for comparison. En face optical coherence tomography angiography imaging (3 × 3 mm scans) with quantitative microvascular analysis of the CC was performed. Main outcome measures were: 1) the percent nonperfused choriocapillaris area; and 2) the average CC signal void size. RESULTS: We included 21 patients with unilateral Type 3 NV (15 female, 71.5%) and 20 patients with unilateral Type 1 or 2 NV (9 female, 45.0% P = 0.118). Mean ± SD age was 82.1 ± 7.4 years in the unilateral Type 3 patients and 78.3 ± 8.1 in unilateral Type 1/2 NV subjects (P = 0.392). The percent nonperfused choriocapillaris area was 56.3 ± 8.1% in eyes with Type 3 NV and 51.9 ± 4.3% in the fellow eyes (P = 0.016). The average signal void size was also increased in those eyes with Type 3 NV (939.9 ± 680.9 µm), compared with the fellow eyes (616.3 ± 304.2 µm, P = 0.039). The number of signal voids was reduced in the Type 3 NV eyes (604.5 ± 282.9 vs. 747.3 ± 195.8, P = 0.046). The subfoveal choroidal thickness was 135.9 ± 54.2 µm in eyes with Type 3 NV and 167.2 ± 65.4 µm in the fellow eyes (P = 0.003). In addition, the fellow eyes of patients with unilateral Type 3 NV displayed more significant CC flow abnormalities versus the fellow eyes with unilateral Type 1/2 NV (percent nonperfused choriocapillaris area = 51.9 ± 4.3% vs. 46.0 ± 2.1%, respectively, P < 0.0001; and average signal void size 616.3 ± 304.2 µm versus 351.4 ± 65.5 µm, respectively, P < 0.0001; and number of signal voids 747.3 ± 195.8 vs. 998.5 ± 147.3, respectively, P < 0.0001). CONCLUSION: Eyes with unilateral Type 3 NV illustrated increased CC nonperfusion versus fellow nonneovascular eyes. These results suggest that choroidal ischemia may play an important role in the development of Type 3 NV.

Retinal Penetration of Intravitreally Injected Tissue Plasminogen Activator: A Rat Model Study.

PURPOSE: To determine whether intravitreal unconjugated tissue plasminogen activator (tPA) (alteplase) can penetrate the intact neural retina and reach the subretinal space in an experimental model. METHODS: This study was performed in 24 Sprague-Dawley rats aged 12 weeks. Under general anesthesia, the right eye was injected with either 0.75 µg of 3 µL tPA (14 rats; study group) or saline (10 rats, control group) into the vitreous. Animals were euthanized at 3, 24, and 48 h. The eyes were enucleated, and cryosections were prepared for immunofluorescence staining. Goat anti-tPA antibody was used to detect tPA. RESULTS: In the study group, staining for tPA was detected in the deep retinal layers in all eyes. The staining was deeper and more intense at 3 and 24 h than at 48 h. There was no tPA staining in the retina of eyes injected with saline. CONCLUSIONS: This experimental study shows that unconjugated tPA administered into the vitreous is capable of penetrating the deep retinal layers and the subretinal space. These findings suggest that further clinical research is warranted on the benefits of intravitreal tPA in the treatment of submacular hemorrhage.

Understanding aneurysmal type 1 neovascularization (polypoidal choroidal vasculopathy): a lesson in the taxonomy of 'expanded spectra' - a review.

The term aneurysmal type 1 neovascularization is derived from terminology, which is established in the literature but has fallen out of use. We believe that aneurysmal type 1 neovascularization accurately describes the lesions which define the entity known as polypoidal choroidal vasculopathy (PCV). Over the last three decades, the clinical spectrum of PCV has expanded to recognize the occurrence of the aneurysmal (polypoidal) lesions in different contexts, resulting in a complex and unwieldy taxonomy based sometimes on circumstantial findings rather than mechanistic considerations. Advances in multimodal imaging provides increasingly convincing evidence that the lesions which define various forms of PCV are indeed vascular and arise from type 1 neovascular networks. The understanding of PCV as type 1 neovascularization with aneurysms renews focus on the question as to why some patients with type 1 neovascularization develop aneurysms while others do not. Conceptual themes and potential for further study are discussed.

Efficacy of topical aflibercept versus topical bevacizumab for the prevention of corneal neovascularization in a rat model.

The aim of this experimental study was to compare the efficacy of topical aflibercept and topical bevacizumab in preventing corneal neovascularization. A chemical burn was created in the right central cornea of male Sprague-Dawley rats, followed immediately by instillation of one drop (25 mg/ml, 20 µl volume) of aflibercept (15 eyes), bevacizumab (14 eyes), or saline (15 eyes). Treatment was repeated twice daily for 7 days. Corneal neovascularization was determined using corneal photographs (ImageJ) on days 1, 4, 7, 10, and histological and immunofluorescence studies, on day 10. Stromal immunoreactivity was evaluated 2 days after injury in 6 rats treated singly with bevacizumab or aflibercept. Corneal neovascularization was observed clinically on day 4 in all groups. In the aflibercept group, the area of neovascularization increased from 7.38 ± 2.23% on day 4 to 21.73 ± 14.59% on day 7 and 31.0 ± 23.61% on day 10. Corresponding values in the bevacizumab group were 6.04% ± 1.81%, 51.27 ± 15.50%, and 54.4 ± 11.33%, and in the control group, 8.99 ± 1.93%, 42.6 ± 19.59%, and 55.15 ± 11.54%. The area of neovascularization was significantly smaller on days 7 and 10 in the aflibercept group than in the control and bevacizumab groups (P < 0.001, all analyses), with no significant differences between the latter two groups (day 7, P = 0.868; day 10, P = 0.213). Clinical findings were compatible with the histological data and supported by immunofluorescence and corneal flat-mount staining. Both drugs demonstrated variable penetration into the corneal stroma. Topical aflibercept effectively inhibits corneal neovascularization in a rat model of chemical burn. These findings may have important therapeutic implications for humans.