Purpose: Anatomical surgical outcomes for the treatment of retinal detachment (RD) are outstanding; however, only 50% of the patients with a detached macula regain 5/10 or better vision. Thus, to ...preserve or restore visual function in RD, several gaps in our understanding of the pathophysiology of the disease need to be bridged. Therefore, the purpose of the current study, was to investigate the anatomical/morphological changes of retinal interneurons and retinal ganglion cells (RGCs) in an experimental model of RD.
Methods: Experimental RD was induced in C57BL6/J mice by a subretinal injection of 1% sodium hyaluronate. Following RD, mice were euthanized at 1‐, 3‐, 7‐, 30‐ and 90‐days post‐surgery and eyes or retinas were isolated and proceed for sectioning or retinal whole mounts respectively. Immunofluorescence and electron microscopy studies were performed against protein kinase C alpha (PKC‐α) to target rod bipolar cells, calretinin and calbindin D to target horizontal cells and brain‐specific homeobox/POU domain protein 3A (Brn3a) and neuron‐specific class III beta‐tubulin (β‐tubulin III) to target RGCs.
Results: Three days post‐RD, PKC‐α+ neurons (rod bipolar cells) began to migrate towards the outer nuclear layer (ONL), while 30 days post‐RD they had significantly migrated towards the ONL and displayed irregular distribution of their cell bodies in the inner nuclear layer. Similarly, processes of horizontal cells also migrated towards the ONL, 7 days post‐RD and became more invasive and disoriented after longer‐term detachment (30 days post‐surgery). Moreover, there was a significant increase in the intensity of calbindin D, 30‐days post‐RD. Brn3a/β‐tubulin ΙΙΙ+ RGCs were significantly fewer 30‐ and 90‐days post RD. All retinal neurons that were examined, did not show any noteworthy differences 1 day post RD.
Conclusions: RD resulted in significant anatomical changes in both rod bipolar and horizontal neurons of the retina along with a notable reduction of RGCs. The cellular response of the inner retina and the RGCs of the detached retina might play an important role in the imperfect visual score of an anatomical successful surgical reattachment.
Many activities of daily living rely on reading, thus is not surprising that complaints from presbyopes originate in reading difficulties rather in visual acuity. Here, the effectiveness of ...presbyopia correction with multifocal contact lenses (CLs) is evaluated using an eye-fixation based method of silent reading performance.
Visual performance of thirty presbyopic volunteers (age: 50 ± 5 yrs) was assessed monocularly and binocularly following 15 days of wear of monthly disposable CLs (AIR OPTIX™ plus HydraGlyde™, Alcon Laboratories) with: (a) single vision (SV) lenses – uncorrected for near (b) aspheric multifocal (MF) CLs. LogMAR acuity was measured with ETDRS charts. Reading performance was evaluated using standard IReST paragraphs displayed on a screen (0.4 logMAR print size at 40 cm distance). Eye movements were monitored with an infrared eyetracker (Eye-Link II, SR Research Ltd). Data analysis included computation of reading speed, fixation duration, fixations per word and percentage of regressions.
Average reading speed was 250 ± 68 and 235 ± 70 wpm, binocularly and monocularly, with SV CLs, improving statistically significantly to 280 ± 67 (p = 0.002) and 260 ± 59 wpm (p = 0.01), respectively, with MF CLs. Moreover, fixation duration, fixations per word and ex-Gaussian parameter of fixation duration, μ, showed a statistically significant improvement when reading with MF CLs, with fixation duration exhibiting the stronger correlation (r = 0.79, p < 0.001) with improvement in reading speed. The correlation between improvement in VA and reading speed was moderate (r = 0.46, p = 0.016), as was the correlation between VA and any eye fixation parameter.
Average silent reading speed in a presbyopic population was found improved with MF compared to SV CL correction and was faster with binocular compared to monocular viewing: this was mainly due to the faster average fixation duration and the lower number of fixations. Evaluating reading performance using eye fixation analysis could offer a reliable outcome of functional vision in presbyopia correction.
To contribute to the WHO initiative, VISION 2020: The Right to Sight, an assessment of global vision impairment in 2020 and temporal change is needed. We aimed to extensively update estimates of ...global vision loss burden, presenting estimates for 2020, temporal change over three decades between 1990–2020, and forecasts for 2050.
We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. Only studies with samples representative of the population and with clearly defined visual acuity testing protocols were included. We fitted hierarchical models to estimate 2020 prevalence (with 95% uncertainty intervals UIs) of mild vision impairment (presenting visual acuity ≥6/18 and <6/12), moderate and severe vision impairment (<6/18 to 3/60), and blindness (<3/60 or less than 10° visual field around central fixation); and vision impairment from uncorrected presbyopia (presenting near vision <N6 or <N8 at 40 cm where best-corrected distance visual acuity is ≥6/12). We forecast estimates of vision loss up to 2050.
In 2020, an estimated 43·3 million (95% UI 37·6–48·4) people were blind, of whom 23·9 million (55%; 20·8–26·8) were estimated to be female. We estimated 295 million (267–325) people to have moderate and severe vision impairment, of whom 163 million (55%; 147–179) were female; 258 million (233–285) to have mild vision impairment, of whom 142 million (55%; 128–157) were female; and 510 million (371–667) to have visual impairment from uncorrected presbyopia, of whom 280 million (55%; 205–365) were female. Globally, between 1990 and 2020, among adults aged 50 years or older, age-standardised prevalence of blindness decreased by 28·5% (–29·4 to −27·7) and prevalence of mild vision impairment decreased slightly (–0·3%, −0·8 to −0·2), whereas prevalence of moderate and severe vision impairment increased slightly (2·5%, 1·9 to 3·2; insufficient data were available to calculate this statistic for vision impairment from uncorrected presbyopia). In this period, the number of people who were blind increased by 50·6% (47·8 to 53·4) and the number with moderate and severe vision impairment increased by 91·7% (87·6 to 95·8). By 2050, we predict 61·0 million (52·9 to 69·3) people will be blind, 474 million (428 to 518) will have moderate and severe vision impairment, 360 million (322 to 400) will have mild vision impairment, and 866 million (629 to 1150) will have uncorrected presbyopia.
Age-adjusted prevalence of blindness has reduced over the past three decades, yet due to population growth, progress is not keeping pace with needs. We face enormous challenges in avoiding vision impairment as the global population grows and ages.
Brien Holden Vision Institute, Fondation Thea, Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg.
Reading performance in clinical practice is commonly evaluated by reading 'aloud' and 'as fast as possible' single sentences. Assessing comprehensive silent reading performance using passages, ...composed of multiple sentences, is the preferred reading mode in real-life reading conditions.
The purpose of this study was to compare eye movement-based silent reading performance for standardised short sentences and paragraphs.
A group of 15 young volunteers (age range: 22-36 years) read silently and comprehensively in two sessions: (a) a paragraph with continuous text and (b) standardised short sentences. Text print size was 0.4 logMAR (1.0 M at 40 cm distance). Eye movements during reading were recorded using video oculography (EyeLink II, SR Research Ltd). Data analysis included computation of reading speed, fixation duration, the number of fixations, saccadic amplitude and percentage of regressions. Moreover, frequency distributions of fixation durations were analysed with ex-Gaussian fittings.
Repeatability coefficient in silent reading speed was found better for the paragraph (66 wpm) than for short sentences (88 wpm). The superiority in repeatability coefficient for the corresponding eye movement parameters, i.e. fixation duration (35 vs 73 ms), regressions (10.1 vs. 22.3%) and fixations per word (0.21 vs. 0.37 fpw), was even more pronounced. In addition, a statistically significant improvement with the paragraph was found in average fixation duration (19 ± 26 ms,
= 0.02), regressions (4.2 ± 7.0%,
= 0.04) and ex-Gaussian fixation parameter, τ (82 vs. 111 ms). No statistically significant difference was found between average reading speed with the paragraph (220 ± 59 wpm) and the short sentences (206 ± 57 wpm) (
= 0.11).
Due to their superior repeatability, paragraphs are preferable to short sentences when evaluating silent comprehensive reading. The concurrent recording of eye movement parameters in silent reading further improves variability and could offer an efficient measure of reading performance and a reliable biomarker of visuo-motor function.
Inherited retinal dystrophies (iRDs) are a group of genetically and clinically heterogeneous conditions resulting from mutations in over 250 genes. Here, homozygosity mapping and whole-exome ...sequencing (WES) in a consanguineous family revealed a homozygous missense mutation, c.973C>T (p.His325Tyr), in RCBTB1. In affected individuals, it was found to segregate with retinitis pigmentosa (RP), goiter, primary ovarian insufficiency, and mild intellectual disability. Subsequent analysis of WES data in different cohorts uncovered four additional homozygous missense mutations in five unrelated families in whom iRD segregates with or without syndromic features. Ocular phenotypes ranged from typical RP starting in the second decade to chorioretinal dystrophy with a later age of onset. The five missense mutations affect highly conserved residues either in the sixth repeat of the RCC1 domain or in the BTB1 domain. A founder haplotype was identified for mutation c.919G>A (p.Val307Met), occurring in two families of Mediterranean origin. We showed ubiquitous mRNA expression of RCBTB1 and demonstrated predominant RCBTB1 localization in human inner retina. RCBTB1 was very recently shown to be involved in ubiquitination, more specifically as a CUL3 substrate adaptor. Therefore, the effect on different components of the CUL3 and NFE2L2 (NRF2) pathway was assessed in affected individuals’ lymphocytes, revealing decreased mRNA expression of NFE2L2 and several NFE2L2 target genes. In conclusion, our study puts forward mutations in RCBTB1 as a cause of autosomal-recessive non-syndromic and syndromic iRD. Finally, our data support a role for impaired ubiquitination in the pathogenetic mechanism of RCBTB1 mutations.
Cone-rod degeneration (CRD) belongs to the disease spectrum of retinal degenerations, a group of hereditary disorders characterized by an extreme clinical and genetic heterogeneity. It mainly ...differentiates from other retinal dystrophies, and in particular from the more frequent disease retinitis pigmentosa, because cone photoreceptors degenerate at a higher rate than rod photoreceptors, causing severe deficiency of central vision. After exome analysis of a cohort of individuals with CRD, we identified biallelic mutations in the orphan gene CEP78 in three subjects from two families: one from Greece and another from Sweden. The Greek subject, from the island of Crete, was homozygous for the c.499+1G>T (IVS3+1G>T) mutation in intron 3. The Swedish subjects, two siblings, were compound heterozygotes for the nearby mutation c.499+5G>A (IVS3+5G>A) and for the frameshift-causing variant c.633delC (p.Trp212Glyfs∗18). In addition to CRD, these three individuals had hearing loss or hearing deficit. Immunostaining highlighted the presence of CEP78 in the inner segments of retinal photoreceptors, predominantly of cones, and at the base of the primary cilium of fibroblasts. Interaction studies also showed that CEP78 binds to FAM161A, another ciliary protein associated with retinal degeneration. Finally, analysis of skin fibroblasts derived from affected individuals revealed abnormal ciliary morphology, as compared to that of control cells. Altogether, our data strongly suggest that mutations in CEP78 cause a previously undescribed clinical entity of a ciliary nature characterized by blindness and deafness but clearly distinct from Usher syndrome, a condition for which visual impairment is due to retinitis pigmentosa.
We demonstrate the application of an extended field of view hybrid microscope, integrating distinct optical and photoacoustic (PA) contrast modes, for the precise three-dimensional anatomy ...delineation of the ciliary body/iris structures in healthy rabbit eyes ex vivo. The glutaraldehyde-induced autofluorescence and the intrinsic PA signals provided by each of the employed imaging modalities were characterized by a high spatial complementarity, offering thus rich morphological information regarding the pars plana and pars plicata ciliary body portions, the iris, as well as, the attached zonule fiber strands. The bimodal microscopy approach presented could find application on studies involving the ocular accommodation mechanism or pathological ciliary body conditions, as a powerful diagnostic technique contributing to the understanding of ocular physiology and function.
Silicone oil is used as endotamponade following vitreoretinal surgery to maintain the retina reattached when indicated. This study investigates the hypothesis that silicone oil causes insulation ...effects on the retina by affecting its response to light.
Electrophysiological responses to a flash stimulus were recorded using full-field electroretinography (ERG) and visual evoked potentials (VEP). Recordings were performed in 9 patients who underwent surgery for retinal detachment, before (1–2 days) and after (2–3 weeks) silicone oil removal (SOR) in both the study and the control eye. Flash ERG and VEP recordings were performed according to the ISCEV standard protocol.
Statistically significant differences were found in the study eye in the amplitudes of the ERG responses and their corresponding ratios, i.e. the amplitude after SOR over the amplitude before SOR, in all conditions tested. No differences were observed in the control eye. The mean ratio of photopic ERG response was 3.4 ± 2.4 for the study and 1.0 ± 0.3 for the control eye (p<0.001). The mean ratio of ERG flicker response was 3.1 ± 2.4 and 1.0 ± 0.3, respectively (p = 0.003). Scotopic flash ERG ratio was 5.0 ± 4.4 for the study and 1.3 ± 0.6 for the control eye (p = 0.012). No differences were observed for the amplitude and latency of flash VEP response after SOR.
Silicone oil causes a reduction in flash ERG responses; no effect was found on flash VEP responses. ERGs in eyes filled with silicone oil should not be considered representative of retinal functionality, in contrast to VEPs, which are not affected by silicone oil presence.
Age-related macular degeneration (AMD) remains the leading cause of blindness in developed countries, and affects more than 150 million worldwide. Despite effective anti-angiogenic therapies for the ...less prevalent neovascular form of AMD, treatments are lacking for the more prevalent dry form. Similarities in risk factors and pathogenesis between AMD and atherosclerosis have led investigators to study the effects of statins on AMD incidence and progression with mixed results. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage.
We were interested in studying the effects of high-dose statins, similar to those showing regression of atherosclerotic plaques, in AMD.
Pilot multicenter open-label prospective clinical study of 26 patients with diagnosis of AMD and the presence of many large, soft drusenoid deposits. Patients received 80mg of atorvastatin daily and were monitored at baseline and every 3months with complete ophthalmologic exam, best corrected visual acuity (VA), fundus photographs, optical coherence tomography (OCT), and blood work (AST, ALT, CPK, total cholesterol, TSH, creatinine, as well as a pregnancy test for premenopausal women).
Twenty-three subjects completed a minimum follow-up of 12months. High-dose atorvastatin resulted in regression of drusen deposits associated with vision gain (+3.3 letters, p=0.06) in 10 patients. No subjects progressed to advanced neovascular AMD.
High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs) and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.
•High dose lipophilic statin administration was associated with regression of large soft drusen and vision gain in 10/23 AMD patients.•Duration of treatment before a positive response was observed was usually 1–1.5years.•Patients on high-dose statin appeared to be protected from progression to “wet” neovascular-AMD.
There is a lack of effective therapies for dry age-related macular degeneration (AMD), one of the leading causes of blindness affecting millions. Although AMD shares similarities with atherosclerosis, prior studies on statins and AMD have failed to show improvement. A limitation of these studies has been the heterogeneity of AMD disease and the lack of standardization in statin dosage. Here, we present for the first time evidence that treatment with high-dose atorvastatin (80mg) is associated with regression of lipid deposits and improvement in visual acuity, without atrophy or neovascularization, in high-risk AMD patients.
Purpose
Τo evaluate the evolution of macular atrophy (MA) in patients with neovascular AMD (nAMD), compared with their fellow eyes exhibiting dry AMD (dAMD).
Methods
This retrospective study included ...124 patients from three centers treated with anti-VEGF in their nAMD eye and having dAMD in the fellow eye. Patients without MA at baseline were analyzed to study the time to first MA development. Synchronous and unsynchronous time course of MA was also studied. MA was evaluated using near-infrared images, while all available optical coherence tomography (OCT) images were used to confirm the criteria proposed by the Classification of Atrophy Meetings group for complete MA.
Results
MA first detection in nAMD eyes increased significantly from year 2 to 6 compared to dAMD eyes. Over the study’s follow-up, 45.1% of nAMD-E developed MA, compared to 16.5% of fellow eyes (
p
< 0.001). When MA in the two eyes was compared in a synchronous paired manner over 4 years, nAMD eyes had an average MA progression rate of 0.275 mm/year versus 0.110 mm/year in their fellow dAMD eyes. Multivariate ANOVA revealed significant time (
p
< 0.001), eye (
p
= 0.003), and time-eye interaction (
p
< 0.001) effects. However, when MA did develop in dAMD eyes and was compared in an asynchronous manner to MA of nAMD eyes, it was found to progress faster in dAMD eyes (dAMD: 0.295 mm/year vs. nAMD: 0.176 mm/year) with a significant time-eye interaction (
p
= 0.015).
Conclusions
In this study, a significant difference in MA incidence and progression was documented in eyes with nAMD under treatment, compared to fellow eye exhibiting dAMD. Eyes with nAMD tended to develop more MA compared to fellow dAMD eyes. However, when atrophy did develop in the fellow dAMD eyes, it progressed faster over time compared to MA in nAMD eyes.
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