Photobiomodulation efficacy in age-related macular degeneration: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated. METHODS: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI). RESULTS: We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias. CONCLUSION: This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM's therapeutic potential for dry AMD.

Choroidal nevus through a broader vision: Retinal imaging acquisition captured with Broad Line Fundus Imaging technology.

OBJECTIVE: To describe the peculiarities in imaging acquisition of fourteen patients with choroidal nevus using the Broad Line Fundus Imaging (BLFI) technology. METHODS: Single-center, retrospective, cross-sectional analysis. RESULTS: All images were acquired using the BLFI technology. We have found that choroidal nevus is undetectable in the blue channel (BC) (435-500 nm) and the green channel (GC) (500-585 nm). The only visible changes are related to the drusen, which appeared in BC and GC as light focal dots, correlated to the yellowish foci in the true-color image. On the red channel (RC) (585-640 nm), all lesions revealed the same pattern: a well-defined dark spot, with enhanced contrast, allowing the better visualization, measuring, and characterization of the nevus when compared with the other color channels, including the true-color imaging. CONCLUSION: BLFI application in choroidal nevus might be helpful at presentation, refining the diagnostic reliability, and monitoring, as it allows for better detection of alterations in the lesions. The peculiarities of the choroidal nevus are better assessed when using the RC due to its longer wavelength and deeper penetration in the retina and choroid.

Current practices and profiles of ophthalmologists involved in retinopathy of prematurity care in Brazil.

Retinopathy of prematurity (ROP) care in Brazil varies in availability of resources and infrastructure. A cross-sectional survey was conducted among ophthalmologists of the Brazilian ROP Group (BRA-ROP) to assess the profiles and practices of ophthalmologists involved in ROP care. A total of 78 responses of BRA-ROP participants (79%) were included. Participants were mostly retina experts (64.1%), female (65.4%), and over 40 years of age (60.2%). Eighty-six percent reported following Brazil's ROP screening criteria. Retinal imaging is available to 16.9% of respondents; fluorescein angiography, to 1.4%. For ROP stage 3 zone II (with plus disease), laser treatment was the preferred treatment (78.9%); for aggressive ROP, anti-VEGF was favored (66.2%). There were significant regional differences in treatment choice. Not all respondents continued to follow treated patients after discharge from the neonatal intensive care unit, highlighting an aspect of ROP care in need of improvement.

Alterações retinianas em pacientes com leucemia linfocítica aguda (lla): discussão de tema a partir de relato de caso / Retinal changes in patients with acute lymphocytic leukemia (all): discussion of topic from a case report

RESUMO A Leucemia Linfocitica Aguda (LLA) é uma doença caracterizada por uma alta taxa de sobrevida, porém o número absoluto de crianças que morrem por ela representa uma grande parcela dos casos de óbitos infantis por câncer. A morbidade decorrente de seu tratamento pode deixar sequelas em pessoas com grande expectativa de vida, tornando-se extremamente necessário o entendimento da patogênese desta doença, possibilitando o desenvolvimento de novos tratamentos e diminuição de sequelas provocadas pela doença. O diagnóstico precoce é importante para se evitar complicações oculares que possam levar a baixa de acuidade visual em longo prazo e para avaliação de recaídas de tratamento sendo determinante no direcionamento de condutas.

ABSTRACT The Acute Lymphocytic Leukemia (ALL) is a disease characterized by a high survival rate, but the absolute number of children who die from it represents a large proportion of cases of infant deaths from cancer. The morbidity resulting from its treatment can leave sequelae in people with high life expectancy, making it extremely necessary to understand the pathogenesis of this disease, enabling the development of new treatments and reduction of sequelae caused by the disease. This early diagnosis is important to avoid ocular complications that may lead to low long-term visual acuity and to evaluate treatment relapses and determine the conducts.

Autoimmune Retinopathy, Testing, and Its Controversies.

Purpose of review: The purpose of this revision is to sumarize the most important clinical features of the autoimune retinopathies (AIRs). Recent findings: AIRs are a group of inflammatory conditions affecting the retina characterized by progressive unexplained visual loss, abnormalities and contraction in visual fields, photoreceptor and electroretinographic dysfunction, and the presence of circulating anti-retinal antibodies. The pathogenesis of AIR remains unclear and various antiretinal antibodies have been associated to the disease. The diagnosis of AIR is based on a particular clinical presentation along with the detection of serum antiretinal antibodies. Numerous anti-inflammatory therapeutic alternatives have been described for the treatment of AIR, nevertheless there is no consensus on treatment protocol. Summary: Because of its association with different types of malignant tumors, the early diagnosis, multi-disciplinary approach and prompt treatment should be warranted.

Impact of manual correction over automated segmentation of spectral domain optical coherence tomography.

OBJECTIVE: To study the automated segmentation of retinal layers using spectral domain optical coherence tomography (OCT) and the impact of manual correction over segmentation mistakes. METHODS: This was a retrospective, cross-sectional, comparative study that compared the automated segmentation of macular thickness using Spectralis™ OCT technology (Heidelberg Engineering, Heidelberg, Germany) versus manual segmentation in eyes with no macular changes, macular cystoid edema (CME), and choroidal neovascularization (CNV). Automated segmentation of macular thickness was manually corrected by two independent examiners and reanalyzed by them together in case of disagreement. RESULTS: In total, 306 eyes of 254 consecutive patients were evaluated. No statistically significant differences were noted between automated and manual macular thickness measurements in patients with normal maculas, while a statistically significant difference was found in central thickness in patients with CNV and with CME. Segmentation mistakes in macular OCTs were present in 5.3% (5 of 95) in the normal macula group, 16.4% (23 of 140) in the CME group, and 66.2% (47 of 71) in CNV group. The difference between automated and manual macular thickness was higher than 10% in 1.4% (2 of 140) in the CME group and in 28.17% (20 of 71) in the CNV group. Only one case in the normal group had a higher than 10% segmentation error (1 of 95). CONCLUSION: The evaluation of automated segmented OCT images revealed appropriate delimitation of macular thickness in patients with no macular changes or with CME, since the frequency and magnitude of the segmentation mistakes had low impact over clinical evaluation of the images. Conversely, automated macular thickness segmentation in patients with CNV showed a high frequency and magnitude of mistakes, with potential impact on clinical analysis.

Choroidal granuloma caused by Mycobacterium Fortuitum.

BACKGROUND: To report a case of a chronic steroid user male patient who developed local abscesses caused by M. fortuitum and concomitant asymptomatic choroidal granuloma. CASE PRESENTATION: A 37-year-old african-american male with history of use of anabolic drugs and intramuscular mineral oil injections in the upper and lower limbs for 15 years for muscular hypertrophy. He developed intramuscular abscesses with systemic infection, sub-retinal lesions in both eyes and alterations in cerebrospinal fluid suggestive of mycobacteria. Considering these findings, empirical treatment for tuberculosis was started, without success. After several negative cultures of the material drained from the abscesses, finally one of the cultures isolated the agent Mycobacterium Fortuitum. Proper treatment for atypical mycobacteria was initiated with clinical and laboratory improvement. After 6 months the sub-retinal lesions regressed. CONCLUSIONS: A typical choroidal granuloma caused by M. Fortuitum is a rare presentation of the infection and our report showed a good outcome with proper treatment.

Choriocapillaris Hypoperfusion Artifact in OCT Angiography.

BACKGROUND AND OBJECTIVE: To illustrate how optical coherence tomography (OCT) angiography (OCTA) can be misinterpreted if not evaluated along with structural en face OCT to analyze the signal intensity. PATIENTS AND METHODS: Patients with different macular diseases associated with suspicious flow impairment in the choriocapillaris were recruited to be imaged on the RTVue XR Avanti device (Optovue, Fremont, CA) with the Angio Retina mode. En face OCT angiograms, structural en face OCT, and corresponding OCT B-scans with flow signal overlaid were compared to evaluate the correspondence of signal strength to areas of flow reduction in the choriocapillaris. RESULTS: Six eyes from six patients were enrolled. Macular lesions evaluated in this study included acute central serous chorioretinopathy, paracentral acute middle maculopathy, age-related macular degeneration, adult-onset foveomacular vitelliform dystrophy, and branch retinal vein occlusion. In all cases, areas of suspicious flow decrement in the choriocapillaris corresponded to hyporeflective areas in the intensity en face OCT. Thus, a precise confirmation of choriocapillaris flow impairment was not possible. CONCLUSION: It is essential to be aware of the importance of analyzing the structural image alongside with the flow image to interpret flow impairment. This is more important in subretinal pigment epithelial structures such as choriocapillaris and choroid. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:603-610.].

Natural History of Subclinical Neovascularization in Nonexudative Age-Related Macular Degeneration Using Swept-Source OCT Angiography.

PURPOSE: Swept-source (SS) OCT angiography (OCTA) was used to determine the prevalence, incidence, and natural history of subclinical macular neovascularization (MNV) in eyes with nonexudative age-related macular degeneration (AMD). DESIGN: Prospective, observational, consecutive case series. PARTICIPANTS: Patients with intermediate AMD (iAMD) or geographic atrophy (GA) secondary to nonexudative AMD in 1 eye and exudative AMD in the fellow eye. METHODS: All patients were imaged using both the 3×3 mm and 6×6 mm SS OCTA fields of view (PLEX Elite 9000; Carl Zeiss Meditec, Inc, Dublin, CA). The en face slab used to detect the MNV extended from the outer retina to the choriocapillaris, and projection artifacts were removed using a proprietary algorithm. MAIN OUTCOME MEASURES: Prevalence of subclinical MNV and time to exudation with Kaplan-Meier cumulative estimates of exudation at 1 year. RESULTS: From August 2014 through March 2017, 160 patients underwent SS OCTA (110 eyes with iAMD and 50 eyes with GA). Swept-source OCTA identified subclinical MNV at the time of first imaging in 23 of 160 eyes, for a prevalence of 14.4%. Six eyes demonstrated subclinical MNV during the follow-up. Of 134 eyes with follow-up visits, a total of 13 eyes demonstrated exudation, and of these 13 eyes, 10 eyes were found to have pre-existing subclinical MNV. By 12 months, the Kaplan-Meier cumulative incidence of exudation for all 134 eyes was 6.8%. For eyes with subclinical MNV at the time of first SS OCTA imaging, the incidence was 21.1%, and for eyes without subclinical MNV, the incidence was 3.6%. There was no difference in the cumulative incidence of exudation from pre-existing MNV in eyes with iAMD or GA (P = 0.847, log-rank test). After the detection of subclinical MNV, the risk of exudation was 15.2 times (95% confidence interval, 4.2-55.4) greater compared with eyes without subclinical MNV. CONCLUSIONS: By 12 months, the risk of exudation was greater for eyes with documented subclinical MNV compared with eyes without detectable MNV. For eyes with subclinical MNV, recommendations include more frequent follow-up and home monitoring. Intravitreal therapy is not recommended until prospective studies are performed.

Anatomical and functional correlation in Susac syndrome: multimodal imaging assessment.

BACKGROUND: Susac's syndrome (SuS) is an uncommon disease characterized by retinal microangiopathy that may be assessed more accurately with optical coherence tomography angiography (OCTA), a new imaging technique which provides a retinal microvasculature map. The purpose of this case report is to describe the multimodal imaging findings of SuS correlating OCTA with functional tests. CASE PRESENTATION: Retrospective review of one case with clinical and imaging evidence of SuS. Color fundus photograph, fluorescein angiography (FA), OCTA, microperimetry (MP) and visual field (VF) tests were analyzed at the time of presentation and at 1- and 6-month visit following initiation of treatment. The study patient underwent standard treatment for SuS. The patient age was 31 year-old and the baseline visual acuity was 20/60 and 20/20 in the right and left eyes, respectively. At presentation, FA showed branch retinal arterial occlusion within the macular area of the right eye and vascular leakage in the periphery of the left eye. OCTA demonstrated areas of superficial and deep retinal vascular plexuses hypoperfusion in both eyes. The OCTA segmentations in the outer retina and choriocapillaris were normal. The low VF and MP sensitivity signals precisely corresponded to the topography of decreased vascular perfusion seen on the OCTA density map in both eyes. Six months after specific SuS therapy, retinal vascular perfusion showed partial improvement in both eyes. CONCLUSION: OCTA may demonstrate superficial and deep retinal vascular non-perfusion without choriocapillary vasculature changes in SuS. This anatomical information given by OCTA corresponded to points of low sensitivity on functional tests represented by VF and MP.

OCT Angiography: An Upcoming Non-invasive Tool for Diagnosis of Age-related Macular Degeneration.

PURPOSE: To review the most recent findings, characteristics, faults and future perspectives of optical coherence tomography angiography (OCTA) in age-related macular degeneration (AMD). RECENT FINDINGS: In dry AMD, OCTA is useful on the evaluation of choriocapillaris perfusion and detection of naïve quiescent non-exudative choroidal neovascularization (CNV). In wet AMD, OCTA can provide detailed anatomic and morphologic information of CNVs, which may help to understand why and how they develop and become active. In other hand, the many artifacts present in OCTA images may lead to misinterpretation and misdiagnosis. SUMMARY: OCTA is a still developing technology that is able to provide a large amount of anatomic, functional and morphologic information in macular diseases and, particularly, AMD. As the technology evolves, the need of dye-based modalities tends to decrease.

Projection artifact removal improves visualization and quantitation of macular neovascularization imaged by optical coherence tomography angiography.

PURPOSE: To visualize and quantify the size and vessel density of macular neovascularization (MNV) using optical coherence tomography angiography (OCTA) with a projection artifact removal algorithm. DESIGN: Multicenter, observational study. PARTICIPANTS: Subjects with MNV in at least one eye. METHODS: Patients were imaged using either a swept-source OCT angiography (SS-OCTA) prototype system or a spectral-domain OCT angiography (SD-OCTA) prototype system. The optical microangiography (OMAG) algorithm was used to generate the OCTA images. Projection artifacts from the overlying retinal circulation were removed from the OMAG OCTA images using a novel algorithm. Following removal of the projection artifacts from the OCTA images, we assessed the size and vascularity of the MNV. Concurrent fluorescein angiography (FA) and indocyanine green angiography (ICGA) images were used to validate the artifact-free OMAG images whenever available. MAIN OUTCOME MEASURES: Size and vascularity of MNV imaged with OCTA before and after the use of a projection-artifact removal algorithm. RESULTS: A total of 30 subjects (40 eyes) diagnosed with MNV were imaged. Five patients were imaged before and after intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors. Following the use of the projection artifact removal algorithm, we found improved visualization of the MNV. Lesion sizes and vascular densities were more easily measured on all the artifact-free OMAG images. In eyes treated with vascular endothelial growth factor inhibitors, vascular density was reduced in all five eyes after treatment, and in four eyes, the size of the MNV decreased. One of five patients showed a slight increase in lesion size, but a decrease in vascular density. CONCLUSIONS: OCTA imaging of MNV using the OMAG algorithm combined with removal of projection artifacts resulted in improved visualization and measurements of the neovascular lesions. OMAG with projection artifact removal should be useful for assessing the response of MNV to treatment using OCTA imaging.

Fluorescein Angiography Versus Optical Coherence Tomography Angiography in Macular Telangiectasia Type I Treated With Bevacizumab Therapy.

This is a report of microvascular changes seen on fluorescein angiography (FA) and optical coherence tomography angiography (OCTA) in a 47-year-old man with macular telangiectasia Type 1 (MacTel1) after a 7-year bevacizumab (Avastin; Genentech, South San Francisco, CA) treatment course. OCTA allowed for clear visualization of most telangiectasias and aneurysms in the deep capillary plexus, with only few microvascular dilatations in the superficial plexus. In addition, areas of capillary dropout in the superficial and deep vascular plexa located near telangiectasias were documented on OCTA. Serial FA demonstrated reduced number of aneurysms and telangiectasias at the 7-year mark compared to baseline. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:263-266.].

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization.

Purpose: The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). Methods: Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Results: Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003). Conclusions: The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans.

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms.

Purpose: To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Methods: Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 µm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Results: Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). Conclusions: The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

Retinal Microvascular Network and Microcirculation Assessments in High Myopia.

PURPOSE: To investigate the changes of the retinal microvascular network and microcirculation in high myopia. DESIGN: A cross-sectional, matched, comparative clinical study. PARTICIPANTS: Twenty eyes of 20 subjects with nonpathological high myopia (28 ± 5 years of age) with a refractive error of -6.31 ± 1.23 D (mean ± SD) and 20 eyes of 20 age- and sex-matched control subjects (30 ± 6 years of age) with a refractive error of -1.40 ± 1.00 D were recruited. METHODS: Optical coherence tomography angiography (OCTA) was used to image the retinal microvascular network, which was later quantified by fractal analysis (box counting [Dbox], representing vessel density) in both superficial and deep vascular plexuses. The Retinal Function Imager was used to image the retinal microvessel blood flow velocity (BFV). The BFV and microvascular density in the myopia group were corrected for ocular magnification using Bennett's formula. RESULTS: The density of both superficial and deep microvascular plexuses was significantly decreased in the myopia group in comparison to the controls (P < .05). The decrease of the microvessel density of the annular zone (0.6-2.5 mm), measured as Dbox, was 2.1% and 2.9% in the superficial and deep vascular plexuses, respectively. Microvessel density reached a plateau from 0.5 mm to 1.25 mm from the fovea in both groups, but that in the myopic group was about 3% lower than the control group. No significant differences were detected between the groups in retinal microvascular BFV in either arterioles or venules (P > .05). Microvascular densities in both superficial (r = -0.45, P = .047) and deep (r = -0.54, P = .01) vascular plexuses were negatively correlated with the axial lengths in the myopic eye. No correlations were observed between BFV and vessel density (P > .05). CONCLUSIONS: Retinal microvascular decrease was observed in the high myopia subjects, whereas the retinal microvessel BFV remained unchanged. The retinal microvascular network alteration may be attributed to ocular elongation that occurs with the progression of myopia. The novel quantitative analyses of the retinal microvasculature may help to characterize the underlying pathophysiology of myopia and enable early detection and prevention of myopic retinopathy.

Choroidal Thickness and Choroidal Vessel Density in Nonexudative Age-Related Macular Degeneration Using Swept-Source Optical Coherence Tomography Imaging.

Purpose: To analyze the relationship between choroidal thickness and the distribution of choroidal blood vessels in eyes with nonexudative AMD. Methods: Eyes with a diagnosis of nonexudative AMD were imaged using a prototype 100-kHz swept-source (SS) optical coherence tomography (OCT) instrument (Carl Zeiss Meditec, Dublin, CA, USA) with a central wavelength of 1050 nm. We used an OCT cube scan pattern consisting of 512 × 512 A-scans over a 12 × 12 mm retinal area. The eyes were partitioned into two groups based on the presence or absence of reticular pseudodrusen (RPD). All scans were segmented using an automated algorithm. In addition, five eyes from each of the two groups were randomly chosen for manual segmentation. Binary choroidal vessels maps were generated from suitable OCT choroidal slabs, and the relationship between the density of large choroidal vessels and choroidal thickness was analyzed using an Early Treatment Diabetic Retinopathy Study-like target centered on the fovea. Results: Twenty-five eyes were enrolled in each group. The automated algorithm produced accurate choroidal thickness maps with an average difference between the manual and automated segmentations of 13.7 µm. There was a significant and stable correlation between choroidal thickness and choroidal vessel density across the two groups. Both average choroidal thickness and vessel density were significantly lower in eyes with RPD. Conclusions: Our fully automated choroidal segmentation algorithm was able to capture the different patterns of choroidal thickness over a wide area. Choroidal thickness has a clear relationship with the density of large choroid vessels in our sample, irrespective of the presence or absence of RPD.