Long-Term Follow-Up of Brolucizumab in Macular Neovascularization.

INTRODUCTION: The aim of the study was to evaluate functional and anatomical changes in type 1 and type 2 naïve macular neovascularization (MNV) patients treated with brolucizumab injections up to 1 year of treatment (week 48). METHODS: Thirty-eight eyes of 38 patients with active MNV were enrolled at the Ophthalmology Clinic of the University "G. d'Annunzio," Chieti-Pescara, Italy. All patients were scheduled for brolucizumab intravitreal injections as per label, according to the standard HAWK and HARRIER trials guidelines. Enrolled patients underwent complete ophthalmic evaluation, including optical coherence tomography (OCT) and OCT angiography. All measurements were evaluated at baseline and then monthly up to week 48. The main outcome measures were changes in best-corrected visual acuity (BCVA); central macular thickness (CMT); subfoveal choroidal thickness (SCT); pigment epithelial detachment presence and maximum height (PEDMH); intraretinal fluid (IRF) presence, subfoveal subretinal fluid (SSRF) presence and maximum height, macular atrophy area, and neovascular membrane flow area in the slab extending from the outer retina to choriocapillaris (ORCC flow). RESULTS: CMT and BCVA significantly changed in both groups over time. ORCC flow and SCT significantly reduced in both groups over time. Atrophy areas increased from 0 to 0.17 mm2 and from 0 to 0.23 mm2 in type 1 MNV and type 2 MNV patients, respectively. PEDMH reduced in type 1 MNV from 138 µm at T0 to 96 µm at T5. Changes in fluids were noted, with SSRF thickness reduction and IRF changes in both groups. CONCLUSION: Our one-year results of treatment confirm brolucizumab to be efficient and safe in both type 1 and type 2 MNV patients, proposing novel OCT parameters as possible biomarkers of treatment.

Choroidal and Retinal Imaging Biomarkers in Different Types of Macular Neovascularization.

BACKGROUND: The aim of this study was to investigate optical coherence tomography (OCT) and OCT angiography (OCTA) parameters in patients with neovascular age-related macular degeneration (nAMD) and macular neovascularization (MNV) type 1, type 2, and type 3. METHODS: In this retrospective study, 105 treatment-naïve eyes of 105 patients (60 men and 45 women) with a definite diagnosis of active nAMD and MNV of different types and 105 frequency-matched age and gender healthy subjects were evaluated (61 men and 44 women). All subjects underwent a full ophthalmic examination and multimodal imaging assessment, including spectral domain (SD) OCT and OCTA. The main outcome measures were choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), and outer retina to choriocapillaris (ORCC) MNV flow area (ORCCFA). RESULTS: Significant differences were found in terms of CVI, CMT, and ORCCFA between MNV 1 and the two other groups. CVI was significantly different between MNV 1 and healthy control patients (p < 0.001) and between MNV 1 and MNV 2 (p < 0.001). ORCCFA and CMT were significantly different between MNV1 and MNV2 (p < 0.005). The difference in subfoveal CT between the three groups was not statistically significant (p = 0.458). A significant negative correlation was found between CVI and ORCCFA. Furthermore, CVI showed a positive correlation with subfoveal CT.

Optical Coherence Tomography Angiography in Macular Neovascularization: A Comparison Between Different OCTA Devices.

Purpose: The purpose of this study is to compare the ability of 3 optical coherence tomography angiography (OCTA) devices to measure lesion area in patients with macular neovascularization (MNV) with type 1, 2 and mixed neovascularization (NV). Methods: OCTA, fluorescein angiography (FA), indocyanine green angiography (ICGA), and structural optical coherence tomography (OCT) were performed. NV lesion area measurements were performed by two graders. Results: Twenty-eight eyes were included: 20 with NV were classified as type 1, 6 as type 2, and 2 as mixed type. AngioVue and Spectralis detected the NV in 26 out of 28 eyes (92.8%). The intraclass correlation coefficient (ICC) between readers for the three different OCTA with the different slabs was high. The NV area was larger in the outer retina to choriocapillaris (ORCC) and choriocapillaris (CC) images for the AngioVue device and the PLEX Elite device compared to avascular images (P < 0.05). The mean values of the NV area were not significantly different among the three instruments (Friedman test, P > 0.05) for the avascular zone (AV), ORCC, and CC images. Median (interquartile range [IQR]) NV were significantly different among avascular images, ORCC images, and CC images of the AngioVue device (P = 0.046), of the Spectralis device (P = 0.015), and the PLEX Elite device (P < 0.001). Conclusions: The ORCC slabs showed the highest detection rate for NV detection independently to the device used, and swept source (SS)-OCTA measurements of ORCC slabs showed the highest detection rate of NVs compared to the spectral domain (SD)-OCTA. Translational Relevance: It is pivotal to realize how much we can rely on OCTA to make a diagnosis of NV.

Tear Meniscus Imaging by Anterior Segment-Optical Coherence Tomography in Medically Controlled Glaucoma.

PURPOSE: The purpose of this study was to investigate the tear meniscus in medically controlled glaucoma patients (MCGP) using anterior segment-optical coherence tomography (AS-OCT). MATERIALS AND METHODS: Fifty-six MCGP, 24 patients with evaporative dry eye (EDE), and 30 healthy subjects (controls), were enrolled. MCGP were divided into group 1 (14 eyes): ß-blockers; group 2 (14 eyes): prostaglandin analogs; group 3 (28 eyes) ≥2 drugs. Ocular Surface Disease Index (OSDI) questionnaire, tear film break-up time, corneal fluorescein staining, Schirmer Test I, and tear meniscus height (lower and upper: L-TMH, U-TMH) and area (L-TMA, U-TMA) using AS-OCT, were performed. RESULTS: OSDI score was higher (P<0.05) in patients with EDE and in group 3 compared with groups 1, 2, and controls. No significant differences were found between group 3 and patients with EDE for all clinical parameters. L-TMA was significantly lower in groups 1 to 3 (P<0.05) and in EDE patients (P<0.001) compared with controls, and it was lower in group 3 and in EDE patients compared with groups 1 and 2 (P<0.05). L-TMH was lower in groups 1 to 3 and in EDE patients compared with controls (P<0.001), and in EDE patients and in group 3 compared with groups 1 and 2 (P<0.05). U-TMA was lower in EDE and MCGP groups compared with controls (P<0.05). L-TMA and L-TMH negatively correlated with OSDI score (P<0.01, r=-0.379 and P<0.01, r=-0.352, respectively). CONCLUSIONS: AS-OCT permits a noninvasive and reliable tear meniscus imaging in medically controlled glaucoma, depicting the glaucoma-related ocular surface disease as a dry eye disease-like condition. Thus, reduced values of TMH and TMA can be proposed as structural indicators of glaucoma therapy-related ocular surface disease.

In vivo and in vitro results of an automated preloaded delivery system for IOL implantation in cataract surgery.

PURPOSE: To compare the corneal tissue trauma after the use of an automated preloaded injector and a manual injector and assess scanning electron microscope (SEM) and atomic force microscope (AFM) features of both injector cartridges. SETTING: Ophthalmology Clinic and Laboratory of Stem Cells and Regenerative Medicine University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; DESIGN: Prospective randomized clinical study METHODS: Forty eyes of 40 patients for phacoemulsification were divided into two groups: implantation of intraocular lens was performed with AutonoMe automated delivery system (AutonoMe group: 20 eyes) and Monarch III injector system (Monarch group: 20 eyes). In vivo confocal microscopy (IVCM) and anterior segment optical coherence tomography (AS-OCT) were performed before surgery, at 1 h, 1 day and 1 month post-operatively. In addition, SEM and AFM were performed on cartridges of both injector systems after injection of the IOL. RESULTS: A greater increase in central corneal thickness and corneal thickness at the incision site were observed in Monarch group versus AutonoMe group 1 h and 1 day post-operatively (p < 0.05). Endothelial cell count loss was significantly higher in Monarch group compared with AutonoMe group (p < 0.05) at 1 and 24 h. AS-OCT showed less endothelial misalignment at 30 days (p < 0.05), and IVCM showed less tunnel inflammation at all time points (p < 0.05) in AutonoMe group compared with Monarch group; roughness analysis at AFM of the AutonoMe cartridge was significantly lower compared to Monarch D cartridge (p < 0.05). CONCLUSIONS: The AutonoMe injector provided less corneal tissue trauma compared with Monarch III injector. The AutonoMe cartridge showed lower roughness at AFM compared to the Monarch D cartridge.

Anatomical and Functional Changes of the Retina and the Choroid after Resolved Chronic CSCR.

BACKGROUND: To investigate anatomical/functional changes after oral eplerenone therapy for chronic central serous chorioretinopathy (CCSC) in successfully treated eyes and fellow eyes and assess timing of foveal subretinal fluid (SRF) resolution. METHODS: Twenty-one eyes of 21 patients suffering from CCSC with monolateral foveal SRF successfully treated with oral eplerenone were enrolled in this retrospective study (group 1). The fellow eyes (21 eyes; group 2), healthy or affected by CCSC, without foveal SRF were considered in the analysis. A control healthy group was enrolled as well (healthy controls; n = 21). Main outcome measures during follow-up included changes of best corrected visual acuity (BCVA, logMAR), central macular thickness (CMT; µm), SRF (µm), subfoveal choroidal thickness (SFCT; µm), superficial capillary plexus density (SCPD, %), deep capillary plexus density (DCPD, %), and choriocapillaris density (CCD, %) and percentage of eyes showing foveal SRF resolution at different time points. RESULTS: Functional and anatomical parameters significantly improved during the study in group 1. BCVA increased significantly (p < 0.001), while CMT, SFCT, and SRF decreased significantly (p < 0.001; p < 0.001, and p = 0.037, respectively). SCPD, DCPD, and CCD did not show any statistically significant difference during follow-up. In 71.4% of eyes, resolution of SRF was observed within 60 days and in the remaining 28.6%, at 120 days. In fellow eyes, SFCT decreased significantly (p < 0.001), whilst all other parameters did not modify. CONCLUSIONS: Eplerenone treatment in chronic CSCR potentially improves recovery of retinal and choroidal morphology as well as visual acuity gain. A complete resolution of foveal SRF was observed in all eyes during a 4-month follow-up, with most eyes healing at 2 months.

All laser cataract surgery compared to femtosecond laser phacoemulsification surgery: corneal trauma.

The aim of this study was to evaluate corneal tissue trauma after femtosecond laser-assisted cataract surgery (FLACS) and phacoemulsification (femtophaco surgery) compared to FLACS and nanolaser emulsification (all laser surgery). This is a prospective nonrandomized clinical study conducted at the Ophthalmology Clinic, University "G. d'Annunzio" of Chieti-Pescara, Italy, involving forty-two eyes of 42 patients candidates to cataract surgery. Patients were enrolled in two groups: femtophaco surgery (group 1 with 21 eyes) and all laser surgery (group 2 with 21 eyes). Main outcome measures included uncorrected visual acuity and distance corrected visual acuity, corneal endothelial cell count, and corneal thickness at the tunnel site and at the center of the cornea. Best correct visual acuity was not significantly different between the two groups. Postoperatively, a significant decrement of endothelial cell count at the center of the cornea was observed in group 1 compared with preoperative values at 90 days (p < 0.001) while t remained stable in group 2. The central corneal thickness showed a statistically significant increase for both groups that reached a maximum thickness at 7 days and then returned to presurgery levels after 90 days for group 1 and after 60 days for group 2. The tunnel corneal thickness showed a statistically significant increase for both groups that reached a maximum thickness at 7 days, which did not return to presurgery level for group 1 but did return to presurgery levels after 60 days for group 2. All laser surgery induced lower central endothelial cell loss and lower increase of corneal thickness compared to femtophaco surgery.

Association between outer retinal alterations and microvascular changes in intermediate stage age-related macular degeneration: an optical coherence tomography angiography study.

AIMS: To investigate associations between changes in retinal vessels and alterations detected by spectral domain optical coherence tomography (SD-OCT) scans in intermediate stage age-related macular degeneration (AMD). METHODS: Thirty eyes of 30 patients with intermediate dry AMD were enrolled in the study. Of the cohort study, 15 eyes (changes-AMD group) showed OCT changes preceding the development of drusen-associated atrophy. A control group of healthy subjects was selected for statistical comparisons. All patients underwent an ophthalmologic evaluation, including OCT angiography (OCTA) and SD-OCT scans. Main outcome measures were superficial vessel density, deep vessel density, macular thickness. RESULTS: Foveal macular thickness was 215.2±32.9 µm in changes-AMD patients and was significantly thinner than no changes-AMD patients (248.3±23.3 µm, p=0.002) and healthy subjects (268.1±19.2 µm, p<0.0001). Furthermore, in the parafoveal area, the thicknesses of both the inner retina and the outer retina were reduced in the changes-AMD group, after comparison with the two other groups. Parafoveal superficial vascular plexus flow density was 43.3±2.7% in changes-AMD patients and was decreased compared with the no changes-AMD group (48.7±3.3%, p=0.003) and healthy controls (50.4±6.1%, p=0.001). A direct correlation of the superficial plexus flow density with the inner retina parafoveal macular thickness (R2=0.761, p=0.028) was found. CONCLUSIONS: We demonstrated an association between SD-OCT signs and retinal blood supply in patients with intermediate AMD and we showed that patients with signs predicting development of geographic atrophy have a reduced flow in superficial vascular plexus and damage of the inner and the outer retina.

Uveo-scleral outflow pathways after ultrasonic cyclocoagulation in refractory glaucoma: an anterior segment optical coherence tomography and in vivo confocal study.

AIMS: To evaluate, using anterior segment optical coherence tomography (AS-OCT) and in vivo confocal microscopy (IVCM), the uveo-scleral aqueous humour (AH) outflow pathways after ultrasonic circular cyclocoagulation (UCCC). METHODS: Forty-four patients with refractory glaucoma underwent 4 or 6 s UCCC (group 1, 24 eyes; group 2, 20 eyes). UCCC was successful when the preoperative intraocular pressure (IOP) reduced by one-third. AS-OCT and IVCM were performed at baseline and at month 1 to evaluate the sclera and conjunctiva. The main outcomes were mean intra-scleral hyporeflective spaces area (MIHSA: mm2) at AS-OCT, mean density and area of conjunctival microcysts (MMD: cysts/mm2; MMA: µm2) at IVCM. The relations between MIHSA, MMA and MMD with IOP were analysed. RESULTS: Mean baseline IOP was 26.9±2.8 mm Hg in group 1 and 27.5±4.0 in group 2. Intra-scleral hyporeflective spaces and microcysts were observed in both groups, without significant differences in MIHSA, MMA and MMD. At month 1, UCCC was successful in 63.6% of patients (41.6% in group 1, 80% in group 2), and IOP reduced to 18.8±3.2 (30.1%) and 17.1±2.7 mm Hg (38.7%), respectively (p<0.001). MIHSA showed a twofold and threefold increase in group 1 and 2 (p<0.05), with a significant difference between groups (p<0.05). MMA and MMD increased in both groups (p<0.05), with values higher in group 2 (p<0.05). Significant relations were found between MIHSA and IOP in both groups (p<0.01). CONCLUSIONS: UCCC induced anatomical modifications of sclera and conjunctiva, which suggested that the trans-scleral AH outflow enhancement is one of the possible mechanisms exploited by ultrasounds to reduce IOP.

AcrySof cachet phakic intraocular lens in myopic patients: visual performance, wavefront error, and lens position.

PURPOSE: To evaluate visual and aberrometric outcomes and position of the AcrySof Cachet (Alcon Laboratories Inc) angle-supported phakic intraocular lens (PIOL) for correction of myopia in adults. METHODS: This prospective study included 36 consecutive eyes with moderate to high myopia in which an AcrySof Cachet PIOL was implanted to minimize refractive error. Follow-up was up to 1 year. RESULTS: Mean manifest spherical equivalent refraction reduced significantly from -14.90 ± 0.90 diopters (D) to -0.29 ± 0.30 D at 1 month and remained stable at 1 year (P<.001). Mean uncorrected distance visual acuity was >0.1 logMAR (20/20 Snellen) in 56% of patients and >0.3 logMAR (20/25 Snellen) in 100% of patients. Corrected distance visual acuity was >0.1 logMAR (20/20 Snellen) in 78% of patients and >0.3 logMAR (20/25 Snellen) in 100% of patients. Mean endothelium-PIOL distance and mean PIOL-crystalline distance were within recommended values at all postoperative evaluations. Statistically significant variations for these variables were not observed. Anterior chamber depth, safety center distance, and vault center distance showed significant reduction after accommodation (P<.01). Anterior chamber depth and safety center distance significantly increased after pupil dilation (P<.01). Mean percentage of endothelial cell loss was 4.04% at 1 year. The root-mean-square of total higher order aberrations and spherical, coma, and trefoil aberrations did not change significantly from pre- to postoperatively. CONCLUSIONS: The AcrySof Cachet PIOL was effective in the correction of moderate to high myopia and provided excellent visual performance with no modification of physiologic ocular wavefront error. Adequate distance from the cornea and crystalline lens was maintained with no significant change during follow-up and under different environmental conditions.

Conjunctival and corneal findings in bleb-associated endophthalmitis: an in vivo confocal microscopy study.

PURPOSE: To report the conjunctival and corneal findings in delayed onset glaucoma filtering bleb-associated endophthalmitis (BAE), by using in vivo confocal microscopy (IVCM). METHODS: This was an observational case series. Four eyes of four glaucomatous patients who previously underwent mytomicin C augmented filtering surgery and affected with delayed onset BAE, underwent IVCM of conjunctival bleb and cornea at diagnosis, after 2 and 8 weeks of therapy. The inflammatory status of the conjunctival epithelium and sub-epithelium was microscopically investigated. Corneal epithelial cells, stromal and endothelial morphology were also evaluated. A group of eight patients with functioning conjunctival filtering bleb was used as control. RESULTS: At diagnosis, a diffuse inflammatory cell infiltration within the conjunctival epithelium presenting evident microcysts was found; conversely, there were no such alterations in the sub-epithelium. An evident stromal oedema, keratocytes activation and diffuse endothelial inflammatory precipitates were the major corneal hallmarks. After 2 weeks of therapy, besides a remarkable improvement of epithelial inflammation and an evident reduction in endothelial precipitates, dendritic cells appeared within conjunctival sub-epithelium and corneal epithelium showed aspects of cellular disruption. After 8 weeks, the conjunctival and corneal features consistently improved, except for the endothelium which still presented high-reflective residual precipitates. CONCLUSIONS: In vivo confocal microscopy proved valuable in the analysis of conjunctival bleb and cornea in patients affected with delayed onset BAE, permitting an evaluation of the course of the disease, the response to therapy and the modulation of dose regimen.

Reliability of nerve fiber layer thickness measurements using optical coherence tomography in normal and glaucomatous eyes.

OBJECTIVE: To evaluate the reliability of nerve fiber layer (NFL) thickness measurements by optical coherence tomography (OCT) in normal and glaucomatous eyes. DESIGN: Prospective, comparative, observational case series and instrument validation study. PARTICIPANTS: Twenty-four glaucomatous patients were compared with 24 gender- and age-matched normal subjects. METHODS: Each individual underwent OCT measurements of NFL thickness. Five repetitions of a series of scans on five separate occasions within a 0.5-month period were performed. Each eye was scanned at three different nerve head programs (1.5 radius [R], R = 1.73 mm, 2.0 R). For each option (1.5 R, R = 1.73 mm, and 2.0R) and region (superior, inferior, temporal, nasal, and overall mean), variance components and intraclass correlation coefficients were determined using repeated measures regression. In these models, NFL thickness, as measured by OCT, was assumed to have three variance components: intersubject, intervisit (within-subject between-dates), and intravisit (within-subject within-date). The intraclass correlation coefficient (intersubject variance/total variance) was used as a measure of reliability. MAIN OUTCOME MEASURES: Measurements of NFL thickness using OCT were performed. RESULTS: Reliability values, as measured by intraclass correlation coefficients, resulted as follows: 1.5 R, 0.54/0.52 (normal/glaucoma); R = 1.73 mm, 0.50/0.50; 2.0 R, 0.49/0.50. CONCLUSIONS: Our results indicate that the recent commercially available OCT provides reliable NFL thickness measurements in both healthy and glaucomatous eyes with each circle radius tested. The greatest amount of variability can be attributed to intersubject differences.

In vivo confocal microscopy in primary congenital glaucoma with megalocornea.

PURPOSE: To report the microscopic findings of congenital glaucoma-related megalocornea using in vivo confocal microscopy. PATIENTS AND METHODS: Two consecutive adult patients presenting the typical features of glaucomatous megalocornea underwent a complete ophthalmologic examination. The first patient presented with progressive glaucoma with bilateral megalocornea. The second patient's left eye was affected by megalocornea without actual evidence of glaucoma, whereas the right eye was healthy. Both patients were examined using a new-generation scanning slit corneal confocal microscope. RESULTS: In both patients, confocal microscopy revealed a mild reduction of keratocyte density in the mid and rear stroma, a particular abnormal "clew-shaped" morphology of stromal nerves, and the presence of discontinuous hyperreflective structures overhanging the endothelial layer at the level of the Descemet membrane. The endothelium showed severe polymegethism, pleomorphism, and a markedly decreased cell density, and focal cellular lesions were noted. CONCLUSION: Confocal microscopy is a diagnostic tool used to evaluate microscopic aspects of Haab striae and endothelial morphologic changes in glaucomatous megalocornea. Unsuspected alterations, such as nerves abnormalities and focal endothelial tractions by scar tissue, were observed.