To evaluate the accuracy of the macular retinal layer segmentation software of the Spectralis spectral-domain (SD) optical coherence tomography (OCT) device (Heidelberg Engineering, Inc., Heidelberg, ...Germany) to discriminate between healthy and early glaucoma (EG) eyes.
Prospective, cross-sectional study.
Forty EG eyes and 40 healthy controls were included.
All participants were examined using the standard posterior pole and the peripapillary retinal nerve fiber layer (pRNFL) protocols of the Spectralis OCT device. Using an Early Treatment Diagnostic Retinopathy Study circle at the macular level, the automated retinal segmentation software was applied to determine thicknesses of the following parameters: total retinal thickness, inner retinal layer (IRL), macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer (mGCL), macular inner plexiform layer (mIPL), macular inner nuclear layer (mINL), macular outer plexiform layer (mOPL), macular outer nuclear layer (mONL), photoreceptors (PR), and retinal pigmentary epithelium (RPE). The ganglion cell complex (GCC) was determined by adding the mRNFL, mGCL, and mIPL parameters and the ganglion cell layer-inner plexiform layer (mGCL-IPL) was determined by combining the mGCL and mIPL parameters. Thickness of each layer was compared between the groups, and the layer and sector with the best area under the receiver operating characteristic curve (AUC) were identified.
Comparison of pRNFL, IRL, mRNFL, mGCL, mIPL, mGCC, mGCL-IPL, mINL, mOPL, mONL, PR, and RPE parameters and total retinal thicknesses between groups for the different areas and their corresponding AUCs.
Peripapillary RNFL was significantly thinner in the EG group globally and in all 6 sectors assessed (P < 0.0005). For the macular variables, retinal thickness was significantly reduced in the EG group for total retinal thickness, mIRL, mRNFL, mGCL, and mIPL. The 2 best isolated parameters to discriminate between the 2 groups were pRNFL (AUC, 0.956) and mRNFL (AUC, 0.906). When mRNFL, mGCL, and mIPL measurements were combined (mGCC and mGCL plus mIPL), then its diagnostic performance improved (AUC, 0.940 and 0.952, respectively).
Macular RNFL, mGCL-IPL, and mGCC measurements showed a high diagnostic capability to discriminate between healthy and EG participants. However, macular intraretinal measurements still have not overcome standard pRNFL parameters.
Purpose To define the role of increased fundus autofluorescence (FAF), a surrogate for lipofuscin content, as a risk factor for progression of geographic atrophy (GA). Design Prospective natural ...history cohort study, the GAIN (Characterization of geographic atrophy progression in patients with age-related macular degeneration). Methods setting : Single-center study conducted in Barcelona, Spain. patients : After screening of 211 patients, 109 eyes of 82 patients with GA secondary to age-related macular degeneration and a minimum follow-up of 6 months were included. observation procedures : Lipofuscin content was classified independently by 2 masked observers according to FAF patterns described previously. Bivariate, stratified, and multivariable analyses were used to explore the associations between GA growth and independent variables. Mediation analysis was used to evaluate the contribution of FAF patterns to GA progression. main outcome : Progression of GA in mm2 /year as measured with FAF. Results Median follow-up was 18 months (range, 6–42). Median GA growth was 1.61 mm2 /year. FAF, baseline area of atrophy, and time of follow-up were independently associated with GA progression ( P < .004). FAF patterns and baseline area of atrophy were strongly associated ( P < .0001), suggesting potential confounding. Mediation analysis suggested that most of the effect of FAF patterns on GA growth was actually caused by baseline area of atrophy. Conclusions FAF patterns, baseline area of atrophy, and time of follow-up were associated with GA progression. However, FAF patterns seem to be a consequence (not a cause) of enlarging atrophy and their effect on GA progression seems mostly driven by baseline area of atrophy.
Background: The aim of this study was to test the feasibility and safety of subretinal transplantation of human induced pluripotent stem cell (hiPSC)-derived retinal pigment epithelium (RPE) cells ...into the healthy margins and within areas of degenerative retina in a swine model of geographic atrophy (GA). Methods: Well-delimited selective outer retinal damage was induced by subretinal injection of NaIO3 into one eye in minipigs (n = 10). Thirty days later, a suspension of hiPSC-derived RPE cells expressing green fluorescent protein was injected into the subretinal space, into the healthy margins, and within areas of degenerative retina. In vivo follow-up was performed by multimodal imaging. Post-mortem retinas were analyzed by immunohistochemistry and histology. Results: In vitro differentiated hiPSC-RPE cells showed a typical epithelial morphology, expressed RPE-related genes, and had phagocytic ability. Engrafted hiPSC-RPE cells were detected in 60% of the eyes, forming mature epithelium in healthy retina extending towards the border of the atrophy. Histological analysis revealed RPE interaction with host photoreceptors in the healthy retina. Engrafted cells in the atrophic zone were found in a patchy distribution but failed to form an epithelial-like layer. Conclusions: These results might support the use of hiPSC-RPE cells to treat atrophic GA by providing a housekeeping function to aid the overwhelmed remnant RPE, which might improve its survival and therefore slow down the progression of GA.
Treatments for geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), are currently under development. Understanding the natural course is needed for optimal trial design. ...Although enlargement rates of GA and visual acuity (VA) in the short term are known from clinical studies, knowledge of enlargement in the long term, life expectancy, and visual course is lacking.
To determine long-term enlargement of GA.
In this study, participant data were collected from 4 population-based cohort studies, with up to 25 years of follow-up and eye examinations at 5-year intervals: the Rotterdam Study cohorts 1, 2, and 3 and the Blue Mountains Eye Study. Data were collected from 1990 to 2015, and data were analyzed from January 2019 to November 2020.
Area of GA was measured pixel by pixel using all available imaging. Area enlargement and enlargement of the square root-transformed area, time until GA reached the central fovea, and time until death were assessed, and best-corrected VA, smoking status, macular lesions according to the Three Continent AMD Consortium classification, a modified version of the Wisconsin age-related maculopathy grading system, and AMD genetic variants were covariates in Spearman, Pearson, or Mann-Whitney analyses.
Of 171 included patients, 106 (62.0%) were female, and the mean (SD) age at inclusion was 82.6 (7.1) years. A total of 147 of 242 eyes with GA (60.7%) were newly diagnosed in our study. The mean area of GA at first presentation was 3.74 mm2 (95% CI, 3.11-4.67). Enlargement rate varied widely between persons (0.02 to 4.05 mm2 per year), with a mean of 1.09 mm2 per year (95% CI, 0.89-1.30). Stage of AMD in the other eye was correlated with GA enlargement (Spearman ρ = 0.34; P = .01). Foveal involvement was already present in incident GA in 55 of 147 eyes (37.4%); 23 of 42 eyes (55%) developed this after a mean (range) period of 5.6 (3-12) years, and foveal involvement did not develop before death in 11 of 42 eyes (26%). After first diagnosis, 121 of 171 patients with GA (70.8%) died after a mean (SD) period of 6.4 (5.4) years. Visual function was visually impaired (less than 20/63) in 47 of 107 patients (43.9%) at last visit before death.
In this study, enlargement of GA appeared to be highly variable in the general population. More than one-third of incident GA was foveal at first presentation; those with extrafoveal GA developed foveal GA after a mean of 5.6 years. Future intervention trials should focus on recruiting those patients who have a high chance of severe visual decline within their life expectancy.
Purpose. This study aims to find out which tool, fundus autofluorescence (FAF) or spectral domain optical coherence tomography (SD-OCT), is more sensitive in detecting retinal pigment epithelium ...(RPE) demise overlying drusen and can, therefore, help predict geographic atrophy (GA) appearance in Age-Related Macular Degeneration (AMD). Methods. A single-site, retrospective, observational, longitudinal study was conducted. Patients with intermediate AMD (iAMD) (large (>125 μm) or intermediate (63–125 μm) drusen with hyper/hypopigmentation) with a minimum follow-up of 18 months were included. Drusen with overlying incipient RPE atrophy were identified on SD-OCT defined as choroidal hypertransmission or nascent geographic atrophy (nGA). These selected drusen were, then, traced backwards in time to determine if incipient RPE atrophy overlying drusen was observed on FAF (well-demarcated region of absence of autofluorescence) before, simultaneously, or after having detected the first signs of incipient RPE atrophy on SD-OCT. The number of drusen in which signs of incipient RPE atrophy was detected earlier using FAF or SD-OCT was compared. The time elapsed from the identification with the more sensitive method to the other was recorded and analyzed. Results. One hundred and thirty-three drusen in 22 eyes of 22 patients were included. Of these, 112 (84.2%) drusen showed choroidal hypertransmission and 21(15.8%) nGA. Early signs of atrophy overlying drusen were found simultaneously on SD-OCT and FAF in 52 cases (39.1%, 95% CI 30.8–47.9%), earliest on FAF in 51 (38.3%, 95% CI 30.0–47.2%) and first on SD-OCT in 30 (22.6%, 95% CI 15.8–30.6%; p<0.05). Statistically significant differences were found between both techniques (p=0.005), with FAF detecting it earlier than SD-OCT. When RPE atrophy was found first on FAF, the median time to diagnosis with SD-OCT was 6.6 months (95% CI 5.5 to 8.6), while if detection occurred earlier on SD-OCT, the median time until identification with FAF was 12.6 months (95% CI 6.0 to 23.4; p=0.0003). Conclusions. In iAMD cases in which early atrophy overlying drusen is not detected simultaneously in FAF and SD-OCT, FAF was significantly more sensitive. Nevertheless, a multimodal approach is recommended and required to evaluate these patients.
Purpose
To evaluate the efficacy and safety profile of Kahook Dual Blade ab interno trabeculectomy combined with phacoemulsification compared to stand-alone conventional cataract surgery.
Methods
A ...single-center longitudinal, randomized controlled trial was conducted. Patients older than 18 years with coexisting cataract and open-angle glaucoma or ocular hypertension were invited to participate. Preoperative and postoperative clinical data were collected and analyzed preoperatively and at months 1, 3, 6, and 12 after the procedure. Main outcome measures included best corrected visual acuity, intraocular pressure, number of glaucoma medications, endothelial cell count, and standard automated perimetry.
Results
Forty-two eyes from 33 patients were randomly allocated to the combined cataract and KDB (treatment,
n
= 21) or cataract alone (control,
n
= 21) groups. Intraocular pressure decreased from 17.9 ± 3.5 to 16.0 ± 2.2 mmHg and from 17.3 ± 2.5 to 15 ± 3.2 mmHg at the last visit in the treatment and control groups (
p
= 0.47). The use of glaucoma medications was reduced from a median (IQR) 1 (1–2) to 0 (0–0) in the treatment group and from 1 (1–2) to 0 (0–1) in the control group, with no significant differences between groups at the 12-month visit (
p
= 0.47). Best corrected visual acuity, endothelial cell count, and standard automated perimetry remained similar during follow-up in both groups.
Conclusions
In patients with well-controlled, mild-to-moderate glaucoma, adding ab interno trabeculectomy with KDB to phacoemulsification might not be more effective than phacoemulsification alone to reach mid-teens IOP values. Both procedures showed similar safety profiles.
Trial registration
ClinicalTrials.gov Identifier: NCT04202562, December 17, 2019 retrospectively registered
To determine whether foveal swelling exists in patients with foveal sparing and geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD) and to establish the contribution of ...different foveal layers to this condition by use of spectral-domain optical coherence tomography (SD-OCT).
Prospective comparative case series.
We assessed patients from a longitudinal study with foveal sparing and GA secondary to AMD. Of an initial sample of 108 patients, 13 eyes of 10 patients complied with the inclusion criteria to study eyes in which apparent swelling would not be questionable. We used a control group of 13 healthy patients to compare the outcome measurements.
We acquired high-resolution SD-OCT horizontal and oblique B-scans centered at the umbo. Two retinal specialists (J.M., F.T.) independently classified the SD-OCT images.
Difference in foveal center thickness, apparent outer nuclear layer (ONL) thickness, ONL thickness without Henle's fiber layer (HFL), sub-ONL thickness, and retinal thickness at 1000 μm and 3500 μm from the foveal center.
The thickness at the foveal center was similar between patients with apparent foveal swelling (cases) and controls without AMD (226 vs. 227 μm; P = 0.56), but the apparent ONL was thicker in cases than in controls (125 vs. 114 μm; P = 0.02). However, when HFL was excluded from the measurements, there was little difference in the results (74 vs. 73 μm; P = 0.82).
We found neither foveal nor ONL swelling in this study. We observed HFL thickening in foveal sparing secondary to GA, which might be related to swelling of the axons of the photoreceptors, or Müller's cells. We also observed thinning of the retina below the external limiting membrane. The clinical significance of these findings should be addressed by longitudinal studies and may have specific therapeutic implications.
To establish the dose of subretinal sodium iodate (NaIO3) in order to create a toxin-induced large animal model of selective circumscribed atrophy of outer retinal layers, the retinal pigment ...epithelium (RPE), and photoreceptors, by spectral-domain optical coherence tomography (SD-OCT) and immunocytochemistry.
Fifteen male and female healthy Yorkshire pigs received unilateral subretinal escalating doses of NaIO3 under general anesthesia. In all the animals, volumes of 0.1 to 0.2 mL NaIO3 were injected into the subretinal space of the area centralis through a 23/38-gauge subretinal cannula. Control SD-OCTs were performed 1 and 2 months after the surgery, at which time pigs were euthanized and eyes enucleated. Globes were routinely processed for histologic and immunohistochemical evaluation.
Spectral-domain OCT and immunohistochemistry revealed circumscribed and well-demarcated funduscopic lesions, limited to the outer retinal layers in pigs treated with 0.01 mg/mL subretinal sodium iodate.
The swine model of a controlled area of circumscribed retinal damage, with well-delimited borders, and selectively of the outer layers of the retina presented herein shows several clinical and histologic features of geographic atrophy in AMD. Therefore, it may represent a valuable tool in the investigation of new emerging regenerative therapies that aim to restore visual function, such as stem cell transplantation or optogenetics.
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