Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME.

Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.

Retinal vascular occlusion in patients with the Covid-19 virus.

BACKGROUND: The coronavirus disease (COVID-19) can cause acute respiratory distress syndrome with dyspnea, anosmia, fever, and cough. Few studies describing ocular findings have been reported. The current case series, reports the clinical findings and natural history of patients with retinal vascular occlusion after COVID-19 infection. CASE PRESENTATIONS: Patients from multiple Brazilian hospitals who had clinical and laboratory diagnoses of COVID-19 with retinal vein or arterial occlusion were analyzed retrospectively. The baseline demographics, clinical presentations of COVID-19, comorbidities, risk factors for thromboembolic events, and use of anticoagulant drugs were reviewed. The relevant clinical findings associated with the retinal vascular occlusive event, management, and outcomes were reported. Fourteen cases of retinal vascular occlusion within 3 months of the laboratory confirmed COVID-19 infection were identified. Three of which required hospitalization for COVID-19 management. Eight cases had central retinal vein occlusion, three branch retinal vein occlusion, one hemispheric retinal vein occlusion, and two central arterial occlusion. The mean patient age at presentation was 48 years; the visual acuity ranged from light perception to 20/20. Nine patients received intravitreal injections of anti-angiogenic drugs and one received ketorolac tromethamine drops for the management of secondary macular edema; four were untreated. CONCLUSIONS: COVID-19 patients may rarely have ocular manifestations of the disease. It was presented a case series of vascular occlusion events that may be related to COVID-19 infection, since these thrombotic events are actively involved in the disease pathophysiology. These cases emphasize the need for further investigation of ocular complications associated with this disease.

Development of a new tissue injector for subretinal transplantation of human embryonic stem cell derived retinal pigmented epithelium.

BACKGROUND: Subretinal cell transplantation is a challenging surgical maneuver. This paper describes the preliminary findings of a new tissue injector for subretinal implantation of an ultrathin non-absorbable substrate seeded with human embryonic stem cell-derived retinal pigment epithelium (hESC-RPE). METHODS: Ultrathin Parylene-C substrates measuring 3.5 mm × 6.0 mm seeded with hESC-RPE (implant referred to as CPCB-RPE1) were implanted into the subretinal space of 12 Yucatan minipigs. Animals were euthanized immediately after the procedure and underwent spectral domain optical coherence tomography (SD-OCT) and histological analysis to assess the subretinal placement of the implant. Evaluation of the hESC-RPE cells seeded on the substrate was carried out before and after implantation using standard cell counting techniques. RESULTS: The tissue injector delivered the CPCB-RPE1 implant through a 1.5 mm sclerotomy and a 1.0-1.5 mm retinectomy. SD-OCT scans and histological examination revealed that substrates were precisely placed in the subretinal space, and that the hESC-RPE cell monolayer continued to cover the surface of the substrate after the surgical procedure. CONCLUSION: This innovative tissue injector was able to efficiently deliver the implant in the subretinal space of Yucatan minipigs, preventing significant hESC-RPE cell loss, minimizing tissue trauma, surgical complications and postoperative inflammation.

The Use of Vital Dyes during Vitreoretinal Surgery - Chromovitrectomy.

The aim of this article is to present the current data with regard to the application of vital dyes during vitreoretinal surgery, 'chromovitrectomy', as well as to overview the current literature regarding the properties of dyes, techniques of application, indications and complications in chromovitrectomy. It is well known that indocyanine green is toxic to the retina and consequently not the ideal dye for chromovitrectomy. Different vital dyes has been tested for chromovitrectomy including trypan blue, patent blue, triamcinolone acetonide, infracyanine green, sodium fluorescein and brilliant blue. Brilliant blue seems to be the ideal dye for internal limiting membrane due to its afinity, lower toxic profile and to reduce the appearance of apoptosis. Besides the dye itself, the injection technique is crucial to avoid additional toxicity, slow injection, far from the retina and protection of the macular hole are some tips. More recently the use of dyes has been applied to stain perfluorcarbon liquids that may enhance its visualization during vitrectomy.

Association Between Growth of Geographic Atrophy and the Complement Factor I Locus.

The association between the growth of geographic atrophy (GA) and a single nucleotide polymorphism (SNP) in the complement factor I (CFI) locus was investigated in the COMPLETE trial. Growth of GA at 52 weeks in eyes without the CFI at-risk allele was slightly faster than the growth in eyes with the CFI at-risk allele (P ≥ .72). The authors of the current study found that in contrast to the faster growth rate reported in CFI-positive eyes from the MAHALO trial, the CFI positive eyes in the COMPLETE trial did not grow faster, and this analysis included 24 eyes that met the MAHALO eligibility criteria.

Comparison of Geographic Atrophy Growth Rates Using Different Imaging Modalities in the COMPLETE Study.

BACKGROUND AND OBJECTIVE: To compare the measurements and growth rates of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) obtained using different imaging modalities. PATIENTS AND METHODS: Thirty patients with AMD and GA measuring from 1.25 mm² to 18 mm² based on spectral-domain optical coherence tomography (SD-OCT) fundus imaging were enrolled. Imaging was performed at baseline and at follow-up months 3, 6, 9, and 12, including autofluorescence (AF) imaging with a fundus camera-based flash system (TRC-50DX; Topcon Medical Systems, Oakland, NJ; AF excitation λ: 535-585 nm; detection λ: 605-715 nm), AF and fluorescein angiography (FA) imaging with a confocal scanning laser ophthalmoscopy (SLO) system (Spectralis; Heidelberg Engineering, Heidelberg, Germany; AF excitation λ: 488 nm; detection λ: > 500 nm), and SD-OCT en face imaging (Cirrus; Carl Zeiss Meditec, Dublin, CA). RESULTS: Average baseline square root measurements and enlargement rates of square root areas appeared similar across all modalities; 0.2 mm was the largest difference between any pair of measurement means. The intraclass correlation coefficients (ICC) were essentially equal to 1 for all comparisons of area measurements but were lower for growth rates than area measurements. Comparison of 26-week average enlargement rates showed no significant difference between the SLO AF image and enhanced SD-OCT en face image (mean difference: 0.01 mm; SD: 0.10; P = .70). CONCLUSION: Agreement among all imaging modalities in measuring the areas of GA at baseline diminished when the growth rates of GA were compared over 26 weeks, likely because each imaging technique identifies different anatomic features along the border of GA, which may appear similar but change at different rates.

Retinal biocompatibility of brilliant blue g with deuterated water for chromovitrectomy.

PURPOSE: To investigate the retinal biocompatibility of Brilliant Blue G with deuterated water (BBG-D2O) as a vital dye for chromovitrectomy. METHODS: In this animal study, 0.05 mL of 0.25 g/L Brilliant Blue G (BBG) associated with 0.13 mL/mL of deuterium oxide (D2O) was injected intravitreally in the right eye and the same amount of balanced salt solution (BSS) was injected similarly in the left eye of rabbits. Clinical examination and histology with light microscopy were performed after seven days. Retinal cell layers were evaluated for morphologic alterations. Electroretinographic (ERG) changes were also assessed at baseline and 7 days after the injections. RESULTS: A total of 6 rabbits were included in the study. The gross histopathologic appearance of the retina, choroid, sclera and optic nerve was within normal limits without any sign of severe retinal necrosis or cystic degeneration. Light microscopy showed that BBG-D2O caused no substantial alterations in retinal layers as compared to control eyes. The injection of BBG-D2O did not induce considerable functional ERG alterations. CONCLUSION: Intravitreal injection of BBG-D2O 0.25 g/L seems to induce no retinal toxicity as documented by lack of functional and histological changes.

Safety and efficacy of various concentrations of topical lidocaine gel for intravitreal injection.

INTRODUCTION: Intravitreal injection (IVT) is one of the most common vitreoretinal procedures, a large majority are performed with local anesthesia. The purpose of this study was to investigate the safety to the cornea and anesthetic efficacy of five concentrations of lidocaine gel. METHODS: A prospective clinical trial was conducted testing lidocaine gel in five preparations: 2, 3.5, 5, 8 and 12%. Patients with macular degeneration, diabetic edema or retina vein occlusion were scheduled for intravitreal treatment received topical anesthesia with lidocaine gel 5 and 10 min before the procedure. Patients answered the visual analog scale for pain during the procedure. Corneal and conjunctival was evaluated using the Oxford scale. RESULTS: In total, 260 patients were randomized into five groups. The mean pain scores (± standard deviation) were 2.63 (± 1.68) in the 2% group, 2.08 (± 1.35) in the 3.5%; 2.00 (± 1.65) in the 5%, 1.93 (± 1.40) in the 8% and 1.83 (± 1.35) in the 12% group. Mean pain score among all groups was similar (p = 0.077). There was no significant difference between groups in regard to keratitis mean score (p = 0.897). CONCLUSIONS: Lidocaine gel at concentrations from 2 to 12% induced similar anesthetic effect for IVTs, without adverse effects on cornea and conjunctiva.

Development and initial experience with a colored perfluorocarbon liquid for intraocular tamponade in vitreoretinal surgery.

PURPOSE: To present the development and initial experience of a novel colored perfluorocarbon liquid (PFCL) in vitreoretinal surgery. METHODS: This was an experimental laboratory study and prospective human interventional study. F6H8 (Fluoron GmbH) was colored by adding 0.3 g/L blue anthraquinone dye. Subsequently, 20% colored F6H8 was prepared by mixing with perfluorooctane or perfluorodecalin (Fluoron GmbH). The novel product is not yet FDA approved for human application. In the laboratory, the colored PFCL was covered with 1) uncolored PFCL, 2) BSS, and 3) silicone oil. Cell toxicity was evaluated in L929 mouse fibroblasts using a growth inhibition assay. Porcine ex vivo eyes were evaluated after vitrectomy followed by intravitreal and subretinal colored PFCL infusion. A pilot, prospective, noncomparative interventional study was conducted in patients with retinal detachment with proliferative vitreoretinopathy (PVR). RESULTS: The density of the colored PFLC mixture was 1.664 g/cm for perfluorooctane and 1.802 g/cm for perfluorodecalin. There was no relevant cell growth inhibition with any concentration of colored PFCL tested. Experiments in pigs revealed that infusion of the colored PFCL caused neither staining of the internal limiting membrane nor intravitreal residual droplets. In the prospective study, 9 eyes (75%) underwent surgery for rhegmatogenous retinal detachment with at least grade C PVR. The colored PFCL enabled retinal break examination and detection of residual intravitreal droplets in all surgeries. There was no case of separation or leakage of the dye from the PFCL solution that could have caused unwanted staining of the vitreous or epiretinal surface. CONCLUSION: The colored PFCL enabled intraoperative maneuvers such as endolaser use. In addition, removal of the colored PFCL was easily achieved at the end of surgery.

Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To evaluate the change in drusen volume following treatment with eculizumab, a systemic inhibitor of complement component 5. PATIENTS AND METHODS: Single-center, prospective, randomized, double-masked clinical trial. Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 26 weeks. MAIN OUTCOME MEASURE: decrease in drusen volume of at least 50% at 26-week follow-up. RESULTS: Mean drusen cube root volumes were 0.49 mm and 0.47 mm (P = .64) at baseline and 0.51 mm and 0.42 mm (P = .17) at 26 weeks in the eculizumab and placebo groups, respectively. In the placebo group, one eye had a decrease in drusen volume of at least 50% and two eyes developed neovascularization through 26 weeks. CONCLUSION: Systemic complement inhibition with eculizumab did not significantly reduce drusen volume. Drusen growth was dependent on the number of complement at-risk alleles. Future trials should consider the use of a composite clinical trial endpoint in which efficacy is defined by the treatment's ability to prevent drusen growth, neovascularization, and the formation of geographic atrophy over 1 year.

Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study.

PURPOSE: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). DESIGN: Prospective, double-masked, randomized clinical trial. PARTICIPANTS: Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging. METHODS: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. MAIN OUTCOME MEASURES: Change in area of GA at 26 weeks. RESULTS: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55 ± 0.94 and 2.02 ± 0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19 ± 0.12 and 0.18 ± 0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37 ± 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 ± 0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. CONCLUSIONS: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Effect of vital dyes on retinal pigmented epithelial cell viability and apoptosis: implications for chromovitrectomy.

PURPOSE: To investigate the in vitro effect of vital dyes on toxicity and apoptosis in a human retinal pigment epithelial cell line. METHODS: ARPE-19 cells were exposed to brilliant blue (BBG), Evans Blue (EB), bromophenol blue (BroB), indocyanine green (ICG), infracyanine green (IfCG), light green (LG), fast green (FG), indigo carmine (IC) and Congo red (CR). Balanced salt solution was used as the control. Five different concentrations and 2 exposure times were tested. Cell viability was determined by the MTS (1-solution methyl thiazolyl tetrazolium) assay and apoptosis by Bax expression on Western blot. RESULTS: All dyes significantly reduced cell viability after 3 min of exposure at all concentrations (p < 0.01), except for BBG that was safe at concentrations up to 0.25 mg/ml and CR up to 0.05 mg/ml, while LG was safe at all concentrations. Toxicity was higher after 30 min of exposure. Expression of Bax was upregulated after all dye exposures, except BBG; ICG had the highest Bax expression (p < 0.01). CONCLUSIONS: Overall the safest dye was BBG followed by LG, IfCG, FG, CR, IC, BroB, EB and ICG. ICG was toxic at all concentrations and exposure times tested. Moreover, BBG was the only dye that did not induce apoptosis in ARPE-19 cells.

Biochemical analysis and decomposition products of indocyanine green in relation to solvents, dye concentrations and laser exposure.

PURPOSE: To investigate pH, ions, osmolarity and precipitation of indocyanine green (ICG), as well as the profile of ICG decomposition products (DPs) after laser exposure and the interaction with quenchers. METHODS: ICG was diluted in water, 5% glucose (GL) or balanced salt solution (BSS) to achieve concentrations of 2.5, 1, 0.25 and 0.1 mg/ml. Osmolarity, pH and precipitation were analyzed immediately and after 24 h. Precipitation analyses were done with a scanning electron microscope. Anion and iodate analyses of ICG and infracyanine green (IfCG) were performed by capillary zone electrophoresis. With regard to DPs, 0.5 mg/ml of ICG was assessed with high-performance liquid chromatography (HPLC) after 810-nm laser irradiation. DP profiles were evaluated with ICG dilution in quenchers (Trolox, histidine and DABCO) in 3 concentrations (0.1, 1 and 10 M). RESULTS: BSS promoted iso-osmotic ICG solutions of 208 mOsm (147-266) compared to GL with 177 mOsm. BSS solutions had a higher physiological pH of 7.2 compared with the GL one of 6.55. ICG precipitated more when diluted with BSS (5.95 mg); in contrast, GL showed less precipitate (3.6 mg). IfCG has no iodine derivates and other ICGs have an average 4.6% of iodate derivates. From HPLC analysis, 5 DPs were observed. The rate of DPs was higher when BSS was used (p < 0.05). Five DPs have been generated with ICG, and they may be altered with the quenchers DABCO, histidine and Trolox. CONCLUSIONS: BSS dilution induces more precipitation and DPs. ICG dilution in any solvent induces DPs. Quencher use reduces the amount of toxic DPs.

Staining properties of brilliant blue depending on different incubation times and solvents in humans.

PURPOSE: Intravitreous injection of vital dyes, e.g. brilliant blue (BBG), promotes better visualization of the internal limiting membrane (ILM). This paper investigates the staining properties of BBG depending on different incubation times and 2 types of solvents--5% glucose (GL) or saline solution--in a prospective study in patients. METHODS: This paper investigates various aspects of BBG in various methods. An interventional prospective study was conducted in patients to examine the binding properties of the blue dye diluted in either saline or 5% GL to epiretinal membranes (ERMs) and ILMs. Forty-nine consecutive patients older than 18 years scheduled for macular ERM, vitreomacular traction and macular hole surgeries were prospectively recruited. The primary outcomes of this study were the degree of ILM and ERM staining. The secondary outcomes of the study were the need of reinjection of BBG or any other dye, the ability of BBG to stain the vitreous, and frequency of complications. The staining of the ILM and ERM were graded as no staining, little, moderate or strong staining. RESULTS: There was no correlation between age (p = 0.32) or gender (p = 0.33) in the staining affinity of BBG to either the ILM or ERM. BBG may be an appropriate staining agent for the ILM in the majority (82%) of surgeries; however, in approximately half of the cases (45%) surgeons considered BBG not enough for ERM coloring and visualization. There is a tendency of BBG to stain the ILM better when saline solution is used compared to GL 5%; however, this was not statistically significant (p = 0.64). There was no difference in the staining efficacy of BBG to the ERMs by either solution (p = 0.70), despite the low staining affinity. CONCLUSION: BBG became the state-of-the-art dye for ILM identification. Differences in staining properties may imply that BBG should not be considered as first-line stain for ERM surgery. BBG is effective in ILM staining in over 80% of macular hole surgeries.

Retinal pigmented epithelial cells cytotoxicity and apoptosis through activation of the mitochondrial intrinsic pathway: role of indocyanine green, brilliant blue and implications for chromovitrectomy.

PURPOSE: To investigate the in vitro effect of four vital dyes on toxicity and apoptosis in a human retinal pigment epithelial (RPE) cell line. METHODS: ARPE-19 cells were exposed to brilliant blue (BriB), methyl blue (MetB), acid violet (AcV) and indocyanine green (ICG). Balanced salt solution was used as control. Five different concentrations of each dye (1, 0.5, 0.25, 0.05 and 0.005 mg/mL) and two exposure times (3 and 30 min) were tested. Cell viability was determined by cell count and MTS assay and cell toxicity by LDH assay. Real-time PCR and Western blotting were used to access the apoptosis process. RESULTS: ICG significantly reduced cell viability after 3 minutes of exposure at all concentrations (p<0.01). BriB was safe at concentrations up to 0.25 mg/mL and MetB at concentrations up to 0.5 mg/mL, while AcV was safe up to 0.05 mg/ml, after 3 minutes of exposure. Toxicity was higher, when the cells were treated for 30 minutes. Expression of Bax, cytochrome c and caspase-9 was upregulated at the mRNA and protein level after ICG exposure, while Bcl-2 was downregulated. AcV and MetB were similar to control. However, BriB resulted in upregulation of Bcl-2, an antiapoptotic protein. CONCLUSIONS: The safest dye used on RPE cells was MetB followed by BriB and AcV. ICG was toxic at all concentrations and exposure times tested. Moreover, ICG was the only dye that induced apoptosis in ARPE-19 cells. BriB significantly increased Bcl-2 protein levels, which might protect against the apoptosis process.

Comparison of drusen area detected by spectral domain optical coherence tomography and color fundus imaging.

PURPOSE: To compare the measurements of drusen area from manual segmentation of color fundus photographs with those generated by an automated algorithm designed to detect elevations of the retinal pigment epithelium (RPE) on spectral domain optical coherence tomography (SD-OCT) images. METHODS: Fifty eyes with drusen secondary to nonexudative age-related macular degeneration were enrolled. All eyes were imaged with a high-definition OCT instrument using a 200 × 200 A-scan raster pattern covering a 6 mm × 6 mm area centered on the fovea. Digital color fundus images were taken on the same day. Drusen were traced manually on the fundus photos by graders at the Doheny Image Reading Center, whereas quantitative OCT measurements of drusen were obtained by using a fully automated algorithm. The color fundus images were registered to the OCT data set and measurements within corresponding 3- and 5-mm circles centered at the fovea were compared. RESULTS: The mean areas (± SD [range]) for the 3-mm circles were SD-OCT = 1.57 (± 1.08 [0.03-4.44]); 3-mm color fundus = 1.92 (± 1.08 [0.20-3.95]); 5-mm SD-OCT = 2.12 (± 1.55 [0.03-5.40]); and 5-mm color fundus = 3.38 (± 1.90 [0.39-7.49]). The mean differences between color images and the SD-OCT (color - SD-OCT) were 0.36 (± 0.93) (P = 0.008) for the 3-mm circle and 1.26 (± 1.38) (P < 0.001) for the 5-mm circle measurements. Intraclass correlation coefficients of agreements for 3- and 5-mm measurements were 0.599 and 0.540, respectively. CONCLUSIONS: There was only fair agreement between drusen area measurements obtained from SD-OCT images and color fundus photos. Drusen area measurements on color fundus images were larger than those with SD-OCT scans. This difference can be attributed to the fact that the OCT algorithm defines drusen in terms of RPE deformations above a certain threshold, and will not include small, flat drusen and subretinal drusenoid deposits. The two approaches provide complementary information about drusen.

Comparison of geographic atrophy measurements from the OCT fundus image and the sub-RPE slab image.

PURPOSE: To compare two different approaches to measuring areas of geographic atrophy (GA) using spectral-domain optical coherence tomography (SD-OCT). METHODS: Fifty eyes with GA were imaged with an SD-OCT instrument. OCT fundus images and sub- retinal pigment epithelium (RPE) slab images were generated. Three graders manually drew the GA boundaries on both en face images. An automated algorithm was used to segment the GA boundaries from the sub-RPE slabs. RESULTS: The agreement between the three manual measurements on both OCT fundus images (ICC = .998) and sub-RPE slabs (ICC = .999) was excellent. Area measurements from OCT fundus images and sub-RPE slabs were highly correlated. The agreement between manual and automated measurements on the sub-RPE slabs was very good (ICC = .795). CONCLUSION: Both OCT fundus images and sub-RPE slab images proved useful for measuring GA in age-related macular degeneration. The automated algorithm typically provided useful measurements of GA area from the sub-RPE slabs.

Quantitative changes in retinal pigment epithelial detachments as a predictor for retreatment with anti-VEGF therapy.

PURPOSE: To determine if quantitative changes in retinal pigment epithelial detachments (PEDs) predict the need for retreatment in eyes undergoing spectral domain optical coherence tomography (SD OCT)-guided as-needed therapy with anti-vascular endothelial growth factor drugs. METHODS: Patients with vascularized PEDs undergoing SD OCT-guided treatment with anti-vascular endothelial growth factor drugs were retrospectively identified. The decision to retreat these cases was based on qualitative assessments of fluid in the macula. Spectral domain OCT images from visits in which the treatment was withheld were retrospectively analyzed. A novel algorithm was then used to measure the area and volume of PEDs at these visits. RESULTS: Fourteen eyes were identified, and retreatment was withheld at 57 visits. When the SD OCT algorithm was used to evaluate the scans from these visits, the PED volume increased at eight visits. At all of these eight visits, a treatment was needed at the next follow-up visit. For the remaining 49 visits in which the treatment was withheld, the PED volume did not increase and no treatment was needed at the next follow-up visit. CONCLUSION: Quantitation of the change in the PED volume and area may be useful in determining when to retreat eyes undergoing SD OCT-guided as-needed anti-vascular endothelial growth factor therapy.

Identifying the boundaries of retinal pigment epithelial detachments using two spectral-domain optical coherence tomography instruments.

BACKGROUND AND OBJECTIVE: To compare two spectral-domain optical coherence tomography (SD-OCT) instruments in identifying the boundaries of retinal pigment epithelium detachment (PED). PATIENTS AND METHODS: 27 eyes were scanned with Cirrus and Spectralis SD-OCT instruments during a single visit. Two Cirrus scan patterns were used: the 512 × 128 and 200 × 200 covering a 6 × 6 mm (20° × 20°) area. The Spectralis scan pattern consisted of seven B-scans, averaged 51 times, covering a 30° × 5° area. The main outcome measures were the retinal thickness at the foveal center and the number of segmentation failures on the central B-scan. RESULTS: The Spectralis algorithm failed to follow the proper retinal contour in 25 eyes (92.6%), while the segmentation on the Cirrus instrument was successful in every central B-scan. Spectralis yielded greater retinal thickness measurements in all cases, and the average difference between Cirrus and Spectralis was 139 µm (P < .001). The intraclass correlation coefficient between the two Cirrus scan patterns was 0.998, and Cirrus versus Spectralis was 0.21. CONCLUSIONS: The Cirrus SD-OCT instrument identifies the appropriate segmentation boundaries in the presence PED. The Spectralis SD-OCT algorithm was unreliable in segmenting PEDs, leading to inaccurate retinal thickness measurements unless manual adjustments were performed.