Topical bromfenac in VEGF-driven maculopathies: topical review and meta-analysis.

BACKGROUND: Topical non-steroidal anti-inflammatory drugs have the potential to reduce treatment burden and improve outcomes of anti-VEGF therapy for a number of retinal disorders, including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. In this review, we focused on the advantages of topical bromfenac as an adjunct to intravitreal anti-VEGF therapy in VEGF-driven maculopathies. METHODS: Cochrane Library, PubMed, and EMBASE were systematically reviewed to identify the relevant studies of neovascular age-related macular degeneration, diabetic macular edema, macular edema associated with retinal vein occlusion, myopic choroidal neovascularization, and radiation maculopathy which reported changes in central retinal thickness, visual acuity, and the number of anti-VEGF injections needed when anti-VEGF therapy was combined with topical bromfenac. RESULTS: In total, ten studies evaluating bromfenac as an adjunct to anti-VEGF therapy were identified. Five studies were included in meta-analysis of the number of injections and five studies were included in the analysis of changes in central retinal thickness. A statistically significantly lower number of intravitreal injections (p = 0.005) was required when bromfenac was used as an adjunct to anti-VEGF therapy compared to anti-VEGF monotherapy with pro re nata regimen. At the same time, eyes receiving bromfenac as an adjunct to anti-VEGF therapy demonstrated non-inferior outcomes in central retinal thickness (p = 0.07). Except for one study which reported better visual outcomes with combined treatment, no difference in visual acuity or clinically significant adverse effects were reported. CONCLUSIONS: This literature review and meta-analysis showed that topical bromfenac can be considered as a safe adjunct to anti-VEGF therapy with a potential to reduce the treatment burden with anti-VEGF drugs requiring frequent injections without compromising improvement of central retinal thickness or visual acuity.

Efficacy and Safety of Cataract Surgery-Assisted Selective Laser Trabeculoplasty: A Pilot Study.

Purpose: To evaluate the intraocular pressure (IOP)-lowering effect and safety of selective laser trabeculoplasty (SLT) with same-day cataract surgery which we named cataract surgery-assisted selective laser trabeculoplasty (CAST) compared to conventional SLT and cataract surgery as standalone procedures. Methods: Patients with primary open-angle glaucoma and cataract were included in this prospective interventional study. All patients received either a CAST procedure, standard SLT, or standard cataract surgery. IOP was assessed at baseline and at months 1, 2, 3, and 6. Topical IOP-lowering medication was canceled during the follow-up if necessary. Results: Twenty-nine, twenty-seven, and thirty eyes received the CAST procedure, SLT, and standard cataract surgery, respectively. There was no statistically significant difference in age, male-to-female ratio, or baseline IOP between groups (P > 0.05). The mean IOP reduction at 6 months after the CAST procedure, SLT, and standard cataract surgery was -7.3 ± 3.8 mmHg, -3.8 ± 3.7 mmHg, and -0.7 ± 3.7 mmHg, respectively (P < 0.001). Eleven out of 29 (37.9%) and 5 out of 27 (18.5%) eyes achieved 30% reduction of IOP after the CAST procedure and SLT, respectively. No eyes achieved 30% reduction of IOP at the end of the follow-up in cataract surgery group. The median number of IOP-lowering medications cancelled after the CAST procedure was 1.0 (range, 0-3). No antiglaucoma medication was cancelled after SLT or cataract surgery. No adverse events were registered in patients who received the CAST procedure. Conclusion: At 6-month follow-up, the CAST procedure had a significantly greater IOP-lowering effect and reduction of topical antiglaucoma medication than SLT or cataract surgery alone.

Labial Mucosa Stem Cells: Isolation, Characterization, and Their Potential for Corneal Epithelial Reconstruction.

Purpose: The purpose of this study was to characterize labial mucosa stem cells (LMSCs) and to investigate their potential for corneal epithelial reconstruction in a rabbit model of total limbal stem cell deficiency (LSCD). Methods: Rabbit LMSCs (rLMSCs) and human (hLMSCs) LMSCs were derived from labial mucosa and characterized in terms of their proliferation activity by the evaluation of proliferation index (PI) and colony forming efficiency (CFE), cell senescence, and differentiation abilities. The expression of various limbus-specific, stem cell-specific, and epithelial markers was assessed via immunocytochemistry. Flow cytometry was used to evaluate mesenchymal and hematopoietic cell surface markers expression. Chromosomal stability of the derived cells was examined using the conventional GTG-banding technique. To assess the impact of LMSCs on corneal epithelial reconstruction, rLMSCs were seeded onto a decellularized human amniotic membrane (dHAM), thereafter their regeneration potential was examined in the rabbit model of total LSCD. Results: Both rLMSCs and hLMSCs showed high proliferation and differentiation abilities, entered senescence at later passages, and expressed different stem cell-specific (ABCB5, ALDH3A1, ABCG2, and p63α), mesenchymal (vimentin), and epithelial (CK3/12, CK15) markers. Cell surface antigen expression was similar to other described mesenchymal stem cells. No clonal structural chromosome abnormalities (CSCAs) and the low percentage of non-clonal structural chromosome abnormalities (NSCAs) were observed. Transplantation of rLMSCs promoted corneal epithelial reconstruction and enhanced corneal transparency. Conclusions: LMSCs have significant proliferation and differentiation abilities, display no detrimental chromosome aberrations, and demonstrate considerable potential for corneal repair.

Surgical outcomes in inferior recurrences of rhegmatogenous retinal detachment.

AIM: To analyze the anatomical and functional outcomes in the inferior recurrences of rhegmatogenous retinal detachment (RRD) depending on the surgical approach. METHODS: Eighty-one eyes of 81 patients (47 males and 34 females with a mean age of 54.8±14.1y) who demonstrated at least one inferior recurrence of RRD were included in this retrospective study. All patients were categorized as having received either circular scleral buckling (SB), pars plana vitrectomy (PPV), a combination of SB and PPV (SB+PPV), PPV with retinotomy (PPV+RT), or PPV+RT and short-term postoperative perfluorocarbon liquid tamponade (PPV+RT+pPFCL). All cases were followed up until successful retinal reattachment or third recurrence. The primary outcome measures were the achievement of the surgical goal without recurrence of RRD and best-corrected visual acuity (BCVA). RESULTS: After the treatment of the first recurrence, the recurrence rate in the PPV+SB group was statistically significantly lower than that of the PPV (P=0.0012), PPV+RT (P=0.028), or PPV+RT+pPFCL (P=0.047) group. There was no statistically significant difference between PPV+SB, PPV+RT, and PPV+RT+pPFCL groups in the recurrence rate after treatment of the second recurrence (42 eyes). However, there was a statistically significant (P=0.016) trend towards a decrease of recurrence rate after PPV+RT+pPFCL. There was no statistically significant improvement of BCVA in either study group (P>0.05) after both first and second recurrence surgery. The mean time follow-up was 109.0±91.0d before the first recurrence and 210.0±186.6d between previous surgery at second recurrence. CONCLUSION: Patients with first inferior recurrence of RRD may benefit from SB as an adjunct to PPV. RT and short-term pPFCL tamponade in the second recurrence may allow better anatomical outcomes, however, without functional improvement.

Status of Choriocapillaris in Fellow Eyes of Patients With Unilateral Retinal Vein Occlusions.

BACKGROUND AND OBJECTIVE: To study the status of the choriocapillaris in fellow eyes of patients with unilateral retinal vein occlusions (RVOs). PATIENTS AND METHODS: Thirty-two healthy eyes of patients with unilateral RVO and 16 eyes of healthy age-matched controls were included. Choriocapillaris flow voids and device-specific choriocapillaris total flow areas were quantified based on 3-mm optical coherence tomography angiography (OCTA) scans and their correlation with the number of resolved para-central acute middle maculopathy (PAMM) lesions on 6-mm OCTA scans was calculated. RESULTS: In fellow eyes of unilateral RVOs and in eyes of healthy individuals, the number of choriocapillaris flow voids was 20.8 ± 5.5 and 13.4 ± 5.4, respectively (P < .001), and choriocapillaris total flow area was 6.0 ± 0.34 mm2 and 6.22 ± 0.13 mm2, respectively (P = .005). The number of resolved PAMM lesions correlates significantly with the number of choriocapillaris flow voids (r = 0.44; P = .002) and with choriocapillaris total flow area (r = -0.52; P < .001). CONCLUSION: Fellow eyes of patients with unilateral RVO demonstrate a substantial decrease of perfusion in choriocapillaris, which correlates with the prevalence of small resolved PAMM lesions. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:23-28.].

SUSPENDED SCATTERING PARTICLES IN MOTION MAY INFLUENCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY VESSEL DENSITY METRICS IN EYES WITH DIABETIC MACULAR EDEMA.

PURPOSE: To study the effect of the suspended scattering particles in motion (SSPiM) on optical coherence tomography angiography (OCTA) vessel density metrics in eyes with diabetic macular edema (DME). METHODS: Thirty-four eyes with DME from 27 patients (16 men and 11 women; 61.4 ± 9.6 years) with DME were included in this retrospective cohort study. Among these eyes, 19 (55.9%) showed the SSPiM artifact on OCTA. All participants received 3-mm and 6-mm optical coherence tomography angiography (OCTA) imaging. Perfusion density and skeletonized vessel density were calculated for the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), and these were compared between eyes with and without SSPiM. Additionally, foveal vessel density in a 300-µm-wide region around the foveal avascular zone (FVD) was evaluated on 3-mm OCTA scans. The main outcome measures were vessel density in the SCP and the DCP. RESULTS: Among the 3-mm OCTA images, there was no statistically significant difference in SCP vessel density in eyes with and without SSPiM (P = 0.98). Vessel density in the DCP (P = 0.001 and P = 0.028 for perfusion and skeletonized vessel density, respectively) and FVD (P = 0.03) on 3-mm OCTA scans were significantly higher in DME eyes with SSPiM than in those without SSPiM. There were no statistically significant differences in vessel density in SCP and DCP between eyes with and without SSPiM based on 6-mm OCTA scans. CONCLUSION: The presence of SSPiM may lead to an overestimation of DCP vessel density in eyes with DME when 3-mm OCTA scans are used for analysis.

Anterior chamber particles are associated with reduction of intraocular pressure after selective laser trabeculoplasty.

PURPOSE: To study the correlation between intraocular pressure (IOP) reduction and the number of hyper-reflective particles appearing in the anterior chamber following selective laser trabeculoplasty (SLT). MATERIAL AND METHODS: In this prospective interventional study, we included primary open-angle glaucoma patients. All participants received a standardised SLT session, which consisted of 100 pulses of 0.9 mJ over 360°. Anterior segment optical coherence tomography (4×4 mm volume scan, 101 horizontal cross-sectional scans) and applanation tonometry were performed before SLT and 15 min, 1 day, 1 week, 1 month and 3 months after. Particles were counted on cross-sectional scans using a standardised algorithm. RESULTS: In this study, we included 25 patients (25 eyes), 14 males and 11 females, with a mean age of 68.9±10.5 and baseline IOP of 21.4±4.5 mm Hg. IOP at month 1 and month 3 after SLT was 18.0±4.0 and 17.4±3.3 mm Hg, respectively. The mean number of anterior chamber particles before and 15 min after SLT was 0.62±0.2 and 7.1±2.0 particles/mm2, respectively (p=0.036). There was a statistically significant correlation between the mean number of anterior chamber particles 15 min after SLT and IOP reduction at 1 month (r=0.62, p=0.03) and 3 months (r=0.71, p=0.01). CONCLUSION: The number of the anterior chamber particles graded using anterior segment optical coherence tomography after the procedure correlates with the IOP-lowering effect of SLT.

Structural en face optical coherence tomography imaging for identification of leaky microaneurysms in diabetic macular edema.

PURPOSE: To study the correspondence between fluorescein angiography (FA) and structural en face optical coherence tomography (OCT) in the identification of leaky microaneurysms in diabetic macular edema (DME). METHODS: Fourteen eyes of eight patients with DME (6 males and 2 females, mean age 67.3 ± 8.5) were included. For all eyes, a 6 × 6 mm structural en face image of the middle retina was obtained and superimposed on a FA image. The reflectivity, capsulation, and association with intraretinal cystic fluid (IRCF) of microaneurysms on en face were evaluated depending on their leaky status on FA. RESULTS: Out of the 320 leaky microaneurysms evaluated, 280 (89.0 ± 8.2%) coincided with those on en face OCT image. Twenty-nine (10.6 ± 6.9%) and 20 (6.5 ± 7.8%) out of all leaky microaneurysms were hyperreflective and demonstrated capsular appearance, respectively. A majority of leaky microaneurysms (97.9 ± 3.2%) were associated with IRCF. From 146 microaneurysms which were found only on en face images, 130 (88.2% ± 15.7%) were hyperreflective, 33 (23.9% ± 15.6%) demonstrated capsular structure, and 13 (9.2% ± 15.0%) demonstrated no associated IRCF. After exclusion of microaneurysms of the inner retina, 95.4 ± 5.4% of leaky microaneurysms were identified on en face image. En face imaging demonstrated 83.5% sensitivity and 89.4% specificity (the area under the curve 0.87) in the identification of leaky microaneurysms. CONCLUSIONS: Structural en face imaging is comparable to FA in identification of leaky microaneurysms in diabetic macular edema. Moderate reflectivity, the absence of capsular structure, and neighboring intraretinal cystic fluid indicate leaky microaneurysms.

Characterization of Choroidal Nevi with Dark-Field Infrared Scanning Laser Ophthalmoscopy.

PURPOSE: To compare dark-field (DF) scanning laser ophthalmoscopy (SLO) against en face OCT and color fundus photography (CFP) in imaging of choroidal nevi and determining lesion area and to describe the characteristics of choroidal nevi using DF SLO. DESIGN: Prospective cohort study. PARTICIPANTS: Multimodal imaging, including DF SLO, OCT, and CFP, was performed in 24 patients (24 eyes; 10 men and 14 women; mean age, 45.1±13.4 years) with choroidal nevi and 14 healthy age-matched volunteers (24 eyes). METHODS: For each imaging method, the area under the receiver operating characteristic curve was constructed to evaluate the ability to identify choroidal nevi. Using DF SLO, each nevus was characterized according to the intensity of the shadow, clarity of the borders, and presence of additional pigmentation. The lesion area was measured by 2 graders for each imaging method. The intraclass correlation coefficient and intergrader correlation coefficient were calculated. MAIN OUTCOME MEASURES: Agreement of DF SLO with CFP and en face OCT in visualization of choroidal nevi. RESULTS: Dark-field SLO showed the highest area under the receiver operating characteristic curve, 1.0, compared with en face OCT and CFP, 0.9 (P = 0.04) and 0.88 (P = 0.025), respectively. Using DF SLO in 17 patients (70.8%) and 7 patients (29.2%), nevus demonstrated dense and partially transparent shadow, respectively. In 10 patients (41.7%) and 14 patients (58.3%), nevus demonstrated sharp and blurred borders, respectively. Additional pigmentation was found in 5 patients (20.8%). The agreement in the evaluation of the area of the nevus between DF SLO and en face OCT and between DF SLO and CFP for grader 1 was 0.89 and 0.95, respectively, and for grader 2 was 0.95 and 0.95, respectively. Weighted κ values in reproducibility analysis for DF SLO, en face OCT, and CFP were 0.8, 0.71, and 0.67, respectively. CONCLUSIONS: Dark-field SLO demonstrated excellent potential for identifying choroidal nevi and was in full agreement with conventional methods in the evaluation of the area of choroidal nevi.

Clinical Application of Fluorescein Angiography-Free Navigated Focal Laser Photocoagulation in Central Serous Chorioretinopathy.

BACKGROUND AND OBJECTIVE: To present clinical application of fluorescein angiography (FA)-free focal laser photocoagulation (FLP) of the leakage point in patients with central serous chorioretinopathy (CSC). PATIENTS AND METHODS: A prospective case series included 16 eyes of 16 patients with non-resolved CSC. The leakage point was identified with optical coherence tomography (OCT) as a small single pigment epithelium detachment (PED) localized in the upper half of the neurosensory detachment with an area of photoreceptor outer segments layer thinning above this PED. FLP was performed with the Navilas 532 system. RESULTS: All patients achieved complete resolution of the subretinal fluid within a mean time of 6.5 ± 1.8 weeks. The mean best-corrected visual acuity statistically significantly increased from 0.08 ± 0.09 (20/25) at baseline to 0.0 ± 0.04 (20/20) at 2 months after FLP (P = .0005). CONCLUSION: FA-free, OCT-guided navigated FLP is an effective and safe option to treat a significant number of patients with CSC. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e118-e124.].

Topography-guided identification of leakage point in central serous chorioretinopathy: a base for fluorescein angiography-free focal laser photocoagulation.

PURPOSE: To identify optical coherence tomography (OCT) findings associated with the leakage points in patients with central serous chorioretinopathy (CSC) to provide fluorescein angiography (FA)-free focal laser photocoagulation (FLP) of the leakage point. METHODS: A retrospective study included 48 patients with CSC (48 eyes). Colocalisation of leakage points with pigment epithelial detachments (PEDs) and with areas of photoreceptor outer segments (PROS) layer thinning was evaluated with OCT. Using FA for each leakage point, the relationship to neurosensory detachment was evaluated with retro-mode confocal scanning laser ophthalmoscopy. RESULTS: Coincidence with PED was found in 52 of 65 (80.0%) leakage points. The PROS thinning was found in 47 of 52 (90.4%) of the PEDs coincided with leakage point. The mean distance from the upper border of neurosensory detachment to the leakage point was 27.3%±13.0% of the vertical dimension of the neurosensory detachment. CONCLUSION: This study demonstrates that PEDs localised in the upper half of the neurosensory detachment area and associated with the PROS thinning area coincided with the leakage point in a significant number of patients with CSC. The patients with non-resolving CSC with a small single PED localising in the upper one-third to one-half of the neurosensory detachment area with an area of PROS thinning above this PED may undergo FA-free OCT-guided FLP treating whole PED.