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Journal Of Clinical & Experimental Ophthalmology[JOURNAL]

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ARC/Arg3.1 expression in the lateral geniculate body of monocular form deprivation amblyopic kittens.

Fan H, Wang Y, Zou Y … +4 more , Song W, Xie J, Tang X, Chen S

BMC Ophthalmol · 2023 Jan · PMID 36597053 · Full text

PURPOSE: The present study compared the expression of activity-regulated cytoskeleton-associated protein (ARC/Arg3.1) in the lateral geniculate body between form deprivation amblyopia kittens and normal kittens to examin... PURPOSE: The present study compared the expression of activity-regulated cytoskeleton-associated protein (ARC/Arg3.1) in the lateral geniculate body between form deprivation amblyopia kittens and normal kittens to examine the significance of ARC/Arg3.1 in the lateral geniculate body in the pathogenesis of amblyopia. METHODS: Twenty kittens were randomly divided into an experimental group (n = 10) and a control group (n = 10). Black opaque covering cloth was used to cover the right eye of kittens in the experimental group. Pattern visual evoked potentials (PVEP) were detected weekly in all kittens. The expression of the ARC/Arg3.1 gene was detected by immunohistochemistry and in situ hybridization, and apoptosis of lateral geniculate body cells was detected by TUNEL. RESULTS: PVEP detection showed that at the age of 5 and 7 weeks, the latency of P100 in the right eye of the experimental group was higher than that of the other three groups (P < 0.05), and the amplitude of P100 was lower than that of the other three groups (P < 0.05). The expression of ARC/Arg3.1 protein (P < 0.05) and mRNA (P < 0.05) in the lateral geniculate body of the experimental group was significantly lower than that of the control group. The level of neuronal apoptosis in the experimental group was higher than that in the control group (P < 0.05). The expression of the ARC/Arg3.1 gene was negatively correlated with the apoptosis level of lateral geniculate body neurons. CONCLUSIONS: The expression of ARC/Arg3.1 is associated with monocular form deprivation amblyopia and apoptosis of lateral geniculate body cells.

Association between whole-grain intake and myopia in chinese children: a cross-sectional epidemiological study.

Liu Z, Wang Q, Zhao Q … +6 more , Gao F, Jin N, Wang D, Wang B, Du B, Wei R

BMC Ophthalmol · 2023 Jan · PMID 36593443 · Full text

BACKGROUND: Nutritional status influences the growth and development of the eyes. However, there are few studies on the association between diet, especially whole grains (WG) consumption, and myopia. The study aimed to e... BACKGROUND: Nutritional status influences the growth and development of the eyes. However, there are few studies on the association between diet, especially whole grains (WG) consumption, and myopia. The study aimed to evaluate the association between WG intake and myopia prevalence among primary school-age children in China. METHODS: This cross-sectional epidemiological study conducted between November 2019 and December 2019 included 586 children, aged 6-12 years, attending primary school in Binhai district, Tianjin, China. Ophthalmologic examinations and optometric cycloplegic refraction measurements were conducted. Information was collected on known risks and protective factors for myopia and the consumption of WGs, vegetables, and fruits. This association between the probability of myopia and the proportion of WG consumption (WG proportion was calculated as the mean intake from WG sources divided by total grain intake), adjusted for protective and risk factors, was analysed using crude and multivariable logistic regression. RESULTS: Among the study participants, 226/586 (38.57%) children had myopia in at least one eye. WG intake was inversely correlated with the prevalence of myopia. Furthermore, in the multivariate analysis, WG intake of > 50% was identified as a protective factor against myopia after subsequent adjustment for children's age, sex, parental myopia, near-work activity, screen time, reading and writing habits, visual fatigue, outdoor time, and classroom light environment (all P < 0.05). CONCLUSION: WG intake (> 50%) was an independent protective factor against myopia. Modifying the form of grains consumed (whole versus refined) could be one of the targets of future public health measures.

Dissociated Optic Nerve Fiber Layer Appearance after Macular Hole Surgery: A Randomized Controlled Trial Comparing the Temporal Inverted Internal Limiting Membrane Flap Technique with Conventional Peeling.

Ehrhardt A, Delpuech M, Luc A … +6 more , Zessler A, Pastor G, Angioi-Duprez K, Berrod JP, Thilly N, Conart JB

Ophthalmol Retina · 2023 Mar · PMID 36109006 · Publisher ↗

PURPOSE: To evaluate the effect of the temporal inverted internal limiting membrane (ILM) flap technique compared with that of conventional ILM peeling on the extent of the dissociated optic nerve fiber layer (DONFL) and... PURPOSE: To evaluate the effect of the temporal inverted internal limiting membrane (ILM) flap technique compared with that of conventional ILM peeling on the extent of the dissociated optic nerve fiber layer (DONFL) and retinal sensitivity in patients undergoing macular hole (MH) surgery. DESIGN: Single-center, prospective, open-label, randomized controlled clinical trial. PARTICIPANTS: Patients requiring vitrectomy for MHs sized > 250 μm. METHODS: Patients were randomly assigned (1:1) to 1 of the following 2 groups: (1) the control group undergoing standard ILM peeling and (2) the experimental group (flap group) undergoing the temporal inverted ILM flap technique. MAIN OUTCOME MEASURES: The primary outcome measure was the total DONFL score at 3 months after surgery. Important secondary outcomes were microperimetry results, primary MH closure rate, external limiting membrane (ELM) and ellipsoid zone (EZ) recovery rates, and best-corrected visual acuity (BCVA). RESULTS: Sixty-five patients were recruited between February 2018 and July 2020; primary outcome data were available for 60 patients. The median DONFL score was 7.0 (3.0-12.5) in the control group and 5.0 (1.5-8.5) in the flap group at 3 months after surgery (P = 0.145). The focal depressions characteristic of the DONFL were limited to the temporal side of the fovea in the flap group, whereas they were found all around the fovea in the control group on spectral-domain OCT images. The MH closure rate (P = 1), EZ and ELM recovery rates (P = 0.252), and BCVA (P = 0.450) were similar between the 2 groups. The 3-month overall median retinal sensitivity (MRS) (P = 0.142) and MRS improvement (P = 0.916) in the control group were comparable with those observed in the flap group. In addition, there was no significant difference between the 2 techniques when considering the temporal area (P = 0.105) or the nasal area (P = 0.468). CONCLUSIONS: The temporal inverted ILM flap technique reduced the extent of the DONFL by preserving the nasal part of the fovea. However, the overall DONFL score was similar between the 2 techniques. In addition, the MRS and BCVA did not differ from those obtained after complete ILM peeling. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The Effect of Macular Hole Duration on Surgical Outcomes: An Individual Participant Data Study of Randomized Controlled Trials.

Murphy DC, Al-Zubaidy M, Lois N … +3 more , Scott N, Steel DH, Macular Hole Duration Study Group

Ophthalmology · 2023 Feb · PMID 36058348 · Publisher ↗

TOPIC: To define the effect of symptom duration on outcomes in people undergoing surgery for idiopathic full-thickness macular holes (iFTMHs) by means of an individual participant data (IPD) study of randomized controlle... TOPIC: To define the effect of symptom duration on outcomes in people undergoing surgery for idiopathic full-thickness macular holes (iFTMHs) by means of an individual participant data (IPD) study of randomized controlled trials (RCTs). The outcomes assessed were primary iFTMH closure and postoperative best-corrected visual acuity (BCVA). CLINICAL RELEVANCE: Idiopathic full-thickness macular holes are visually disabling with a prevalence of up to 0.5%. Untreated BCVA is typically reduced to 20/200. Surgery can close holes and improve vision. Symptom duration is thought to affect outcomes with surgery, but the effect is unclear. METHODS: A systematic review identified eligible RCTs that included adults with iFTMH undergoing vitrectomy with gas tamponade in which symptom duration, primary iFTMH closure, and postoperative BCVA were recorded. Bibliographic databases were searched for articles published between 2000 and 2020. Individual participant data were requested from eligible studies. RESULTS: Twenty eligible RCTs were identified. Data were requested from all studies and obtained from 12, representing 940 eyes in total. Median symptom duration was 6 months (interquartile range, 3-10). Primary closure was achieved in 81.5% of eyes. There was a linear relationship between predicted probability of closure and symptom duration. Multilevel logistic regression showed each additional month of duration was associated with 0.965 times lower odds of closure (95% confidence interval [CI], 0.935-0.996, P = 0.026). Internal limiting membrane (ILM) peeling, ILM flap use, better preoperative BCVA, face-down positioning, and smaller iFTMH size were associated with increased odds of primary closure. Median postoperative BCVA in eyes achieving primary closure was 0.48 logarithm of the minimum angle of resolution (logMAR) (20/60). Multilevel logistic regression showed for eyes achieving primary iFTMH closure, each additional month of symptom duration was associated with worsening BCVA by 0.008 logMAR units (95% CI, 0.005-0.011, P < 0.001) (i.e., ∼1 Early Treatment Diabetic Retinopathy Study letter loss per 2 months). ILM flaps, intraocular tamponade using long-acting gas, better preoperative BCVA, smaller iFTMH size, and phakic status were also associated with improved postoperative BCVA. CONCLUSIONS: Symptom duration was independently associated with both anatomic and visual outcomes in persons undergoing surgery for iFTMH. Time to surgery should be minimized and care pathways designed to enable this.

Diabetic Macular Edema and Diode Subthreshold Micropulse Laser: A Randomized Double-Masked Noninferiority Clinical Trial.

Lois N, Campbell C, Waugh N … +25 more , Azuara-Blanco A, Maredza M, Mistry H, McAuley D, Acharya N, Aslam TM, Bailey C, Chong V, Downey L, Eleftheriadis H, Fatum S, George S, Ghanchi F, Groppe M, Hamilton R, Menon G, Saad A, Sivaprasad S, Shiew M, Steel DH, Talks JS, Doherty P, McDowell C, Clarke M, DIAMONDS Study Group

Ophthalmology · 2023 Jan · PMID 35973593 · Publisher ↗

PURPOSE: To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT... PURPOSE: To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 μm. DESIGN: Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial. PARTICIPANTS: Adults with center-involved DME < 400 μm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes. METHODS: Randomization 1:1 to 577 nm SML or SL treatment. Retreatments were allowed. Rescue with intravitreal anti-vascular endothelial growth factor therapies or steroids was permitted if 10 or more ETDRS letter loss occurred, CRT increased > 400 μm, or both. MAIN OUTCOME MEASURES: Primary outcome was mean change in BCVA in the study eye at 24 months (noninferiority margin 5 ETDRS letters). Secondary outcomes were mean change from baseline to month 24 in binocular BCVA; CRT and mean deviation of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL EQ-5D-5L, 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life-years (QALYs) gained; adverse effects; and number of laser and rescue treatments. RESULTS: The study recruited fully (n = 266); 87% of SML-treated and 86% of SL-treated patients had primary outcome data. Mean ± standard deviation BCVA change from baseline to month 24 was -2.43 ± 8.20 letters and -0.45 ± 6.72 letters in the SML and SL groups, respectively. Subthreshold micropulse laser therapy was deemed not only noninferior but also equivalent to SL therapy because the 95% confidence interval (CI; -3.9 to -0.04 letters) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS letters). No statistically significant difference was found in binocular BCVA (0.32 ETDRS letters; 95% CI, -0.99 to 1.64 ETDRS letters; P = 0.63); CRT (-0.64 μm; 95% CI, -14.25 to 12.98 μm; P = 0.93); mean deviation of the visual field (0.39 decibels (dB); 95% CI, -0.23 to 1.02 dB; P = 0.21); meeting driving standards (percentage point difference, 1.6%; 95% CI, -25.3% to 28.5%; P = 0.91); adverse effects (risk ratio, 0.28; 95% CI, 0.06-1.34; P = 0.11); rescue treatments (percentage point difference, -2.8%; 95% CI, -13.1% to 7.5%; P = 0.59); or EQ-5D, NEI-VFQ-25, or VisQoL scores. Number of laser treatments was higher in the SML group (0.48; 95% CI, 0.18-0.79; P = 0.002). Base-case analysis indicated no differences in costs or QALYs. CONCLUSIONS: Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments.

Impact of the COVID-19 pandemic on individuals with nystagmus and an exploration of public assumptions about the condition: an electronic questionnaire study.

Rennie K, Alagendran R, Lee H … +3 more , Griffiths H, Nystagmus U. K. Eye Research Group (NUKE), Self J

BMC Ophthalmol · 2022 Jun · PMID 35718783 · Full text

PURPOSE: Nystagmus is a disorder characterized by uncontrolled, rhythmic oscillations of the eyes. It often causes reduced visual function beyond reduced visual acuity alone. There is a paucity of literature regarding th... PURPOSE: Nystagmus is a disorder characterized by uncontrolled, rhythmic oscillations of the eyes. It often causes reduced visual function beyond reduced visual acuity alone. There is a paucity of literature regarding the public understanding of nystagmus, and there are no published data on the impact of the COVID-19 pandemic on people living with the condition. This study explores the self-reported impact of the COVID-19 pandemic on those with nystagmus, and examines both public understanding of how nystagmus affects people who have it and the perceptions of public understanding by those with the condition and their carers. METHODS: A qualitative questionnaire was designed following a stakeholder engagement process. This questionnaire was advertised via social media platforms and charity websites to achieve widespread recruitment. Data were collected between November and December 2020. Participants were divided into two groups based on their response to the question: "Do you, or anyone you know well, have nystagmus?". Questions were posed to participants in a purpose-built, branching survey. The resulting data were analyzed using descriptive and inferential statistical methods. RESULTS: One thousand six hundred forty-five respondents were recruited, of which 849 (51.6%) answered "Yes" to the initial filtering question. Analysis showed that, broadly, public understanding of nystagmus differs from the perception of it by those with nystagmus and their carers, that the COVID-19 pandemic has had a significant impact on those with nystagmus, and that respondents who have met someone with nystagmus, even briefly, tend to have a greater understanding of the impact of the condition. CONCLUSION: This study highlights the lack of public awareness regarding nystagmus and suggests opportunities to increase the awareness of nystagmus without the need for extensive knowledge of the condition. The COVID-19 pandemic has posed additional difficulties for those living with nystagmus, which is likely to be comparable among those with similar ocular disorders.

Tilt and decentration of posterior and anterior iris-claw intraocular lenses: a pilot study using anterior segment optical coherence tomography.

Calzetti G, Bellucci C, Tedesco SA … +3 more , Rossi M, Gandolfi S, Mora P

BMC Ophthalmol · 2022 May · PMID 35606746 · Full text

BACKGROUND: Information on the centration and tilt of iris-claw intraocular lenses (IC-IOLs) is limited. In this study, we tested the capacity of an anterior segment optical coherence tomography (AS-OCT) instrument to me... BACKGROUND: Information on the centration and tilt of iris-claw intraocular lenses (IC-IOLs) is limited. In this study, we tested the capacity of an anterior segment optical coherence tomography (AS-OCT) instrument to measure decentration and tilt of anterior and posterior IC-IOLs through an integrated software. METHODS: The present observational, cross-sectional study was conducted at University Eye Clinic of Parma (Parma, Italy). The CASIA2 swept-source AS-OCT (Tomey Corp.) was used to measure the tilt and decentration of posterior and anterior IC-IOLs in patients implanted at least 6 months in advance. After failure with full-automation, semi-manual IOL tracing was applied. In-the-bag (IB) contralateral IOLs, when present, were measured automatically. The Bland-Altman method was used to evaluate the agreement between repeated measurements (2 images for each study eye). The amount and direction of tilt and decentration were recorded and plotted into polar charts for evaluation. RESULTS: A total of 21 patients were included: 14 with posterior and 7 with anterior IC-IOL fixation. In 17 eyes (81%), the AS-OCT provided a repeatable measurement of tilt and decentration. All contralateral eyes with IB IOL were automatically measured. The median decentration was 0.67 mm, 0.24 mm, and 0.24 mm in posterior IC-IOLs, anterior IC-IOLs, and IB IOLs group, respectively. The median tilt was 5.0°, 5.6°, and 5.6° for posterior IC-IOLs, anterior IC-IOLs, and IB IOLs, respectively. Tilt direction was mainly temporal, while decentration was inferior-temporal with posterior IC-IOLs and scattered with anterior IC-IOLs and IB IOLs. CONCLUSIONS: The semi-manual tracing function of the CASIA2 AS-OCT provides repeatable and affordable measurements of the decentration and tilt of IC-IOLs in both the anterior and posterior chamber. Data from the former group were similar to the IB group.

Epiregulin, epigen and betacellulin antibodies and axial elongation in young guinea pigs with lens-induced myopization.

Dong L, Zhang RH, Zhou WD … +6 more , Li YF, Li HY, Wu HT, Shi XH, Jonas JB, Wei WB

BMC Ophthalmol · 2022 Apr · PMID 35477375 · Full text

BACKGROUND: To examine an effect of intravitreally applied antibodies against epidermal growth factor family members, namely epiregulin, epigen and betacellulin, on ocular axial elongation. METHODS: The experimental stud... BACKGROUND: To examine an effect of intravitreally applied antibodies against epidermal growth factor family members, namely epiregulin, epigen and betacellulin, on ocular axial elongation. METHODS: The experimental study included 30 guinea pigs (age:3-4 weeks) which underwent bilateral lens-induced myopization and received three intraocular injections of 20 µg of epiregulin antibody, epigen antibody and betacellulin antibody in weekly intervals into their right eyes, and of phosphate-buffered saline into their left eyes. Seven days after the last injection, the animals were sacrificed. Axial length was measured by sonographic biometry. RESULTS: At baseline, right eyes and left eyes did not differ (all P > 0.10) in axial length in neither group, nor did the interocular difference in axial length vary between the groups (P = 0.19). During the study period, right and left eyes elongated (P < 0.001) from 8.08 ± 0.07 mm to 8.59 ± 0.06 mm and from 8.08 ± 0.07 mm to 8.66 ± 0.07 mm, respectively. The interocular difference (left eye minus right eye) in axial elongation increased significantly in all three groups (epiregulin-antibody:from 0.03 ± 0.06 mm at one week after baseline to 0.16 ± 0.08 mm at three weeks after baseline;P = 0.001); epigen-antibody group:from -0.01 ± 0.06 mm to 0.06 ± 0.08 mm;P = 0.02; betacellulin antibody group:from -0.05 ± 0.05 mm to 0.02 ± 0.04 mm;P = 0.004). Correspondingly, interocular difference in axial length increased from -0.02 ± 0.04 mm to 0.13 ± 0.06 mm in the epiregulin-antibody group (P < 0.001), and from 0.01 ± 0.05 mm to 0.07 ± 0.05 mm in the epigen-antibody group (P = 0.045). In the betacellulin-antibody group the increase (0.01 ± 0.04 mm to 0.03 ± 0.03 mm) was not significant (P = 0.24). CONCLUSIONS: The EGF family members epiregulin, epigen and betacellulin may be associated with axial elongation in young guinea pigs, with the effect decreasing from epiregulin to epigen and to betacellulin.

Long-term Retinal Morphology and Functional Associations in Treated Neovascular Age-Related Macular Degeneration: Findings from the Inhibition of VEGF in Age-Related Choroidal Neovascularisation Trial.

Peto T, Evans RN, Reeves BC … +14 more , Harding S, Madhusudhan S, Lotery A, Downes S, Balaskas K, Bailey CC, Foss A, Ghanchi F, Yang Y, Phillips D, Rogers CA, Muldrew A, Hamill B, Chakravarthy U

Ophthalmol Retina · 2022 Aug · PMID 35314388 · Publisher ↗

PURPOSE: To describe the frequency of long-term morphologic features and their relationships with visual function in participants who exited the Inhibition of VEGF in Age-Related Choroidal Neovascularisation (IVAN; ISRCT... PURPOSE: To describe the frequency of long-term morphologic features and their relationships with visual function in participants who exited the Inhibition of VEGF in Age-Related Choroidal Neovascularisation (IVAN; ISRCTN92166560) trial. DESIGN: Multicenter cohort study up to 7 years after enrollment. PARTICIPANTS: Patients enrolled in the IVAN trial, excluding participants who died or withdrew during the trial. METHODS: Multimodal fundus images, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA) were obtained for a subset of 199 participants who attended a research visit. Clinical sites (n = 20) also provided all visual acuity and clinical information from usual care records for 532 participants and submitted the most recent color, OCT, and other fundus images for 468 participants to a reading center. MAIN OUTCOME MEASURES: Assessed the following from the most recent images: intralesional macular atrophy (ILMA) within the footprint of the neovascular lesion; hyperreflective material (HRM); intraretinal fluid (IRF); subretinal fluid (SRF); pigment epithelial detachment (PED); and disorganized retinal outer layers (DROLs). Cross-sectional relationships between morphologic features and BCVA/LLVA were estimated. RESULTS: Intralesional macular atrophy was present in 31.8% of the study eyes at IVAN exit (mean follow-up, 1.96 years) and 89.5% at the most recent imaging visit (mean follow-up, 6.18 years). Hyperreflective material, IRF, SRF, PED, and DROLs were present in 78.8%, 47.7%, 7.6%, 94.5%, and 55% of the study eyes, respectively. In the subset with complete imaging data, in eyes without DROL, the BCVA was worst in the thinnest outer fovea tertile (thinnest minus middle and thickest tertiles, -19.7 and -19.5 letters, respectively), whereas in eyes with DROL, the BCVA was worst in the thickest (thinnest and middle tertiles minus thickest, 12.5 and 12.2, respectively). Regression models showed that the presence of ILMA and HRM was independently associated with BCVA (22 letters worse [95% confidence interval {CI}, -11.2 to -32.8; P < 0.001] and 9.8 letters worse [95% CI, -0.1 to -19.4; P = 0.047], respectively). Subretinal fluid and foveal PED were associated with better BCVA (5.9 letters [95% CI, -7.9 to 19.7; P = 0.399] and 6.4 letters [95% CI, -1.1 to 14.0; P = 0.094], respectively). The model with LLVA was similar. A sensitivity analysis involving the entire eligible cohort yielded similar estimates. CONCLUSIONS: Macular atrophy and HRM were common after 7 years of follow-up and strongly associated with visual outcomes.

Frequency of Intravitreal Anti-VEGF Injections and Risk of Death: A Systematic Review with Meta-analysis.

Reibaldi M, Fallico M, Avitabile T … +6 more , Marolo P, Parisi G, Cennamo G, Furino C, Lucenteforte E, Virgili G

Ophthalmol Retina · 2022 May · PMID 34974177 · Publisher ↗

TOPIC: To investigate whether an increasing number of intravitreal anti-VEGF injections is associated with a higher mortality risk. CLINICAL RELEVANCE: The issue of systemic safety of intravitreal anti-VEGF therapy has b... TOPIC: To investigate whether an increasing number of intravitreal anti-VEGF injections is associated with a higher mortality risk. CLINICAL RELEVANCE: The issue of systemic safety of intravitreal anti-VEGF therapy has been long discussed. Evidence from meta-analyses of randomized studies has shown no increased risk of mortality in the overall population, whereas some warning signals of higher mortality were found in patients with diabetes exposed to intense and prolonged treatment. Concerns have been raised about whether an increasing number of anti-VEGF injections could be associated with a higher mortality. METHODS: Randomized clinical trials enrolling arms with different intensities of anti-VEGF therapy were searched. The primary outcome measure was the incidence rate ratio (IRR) of death with 95% confidence interval (CI) for receiving 5 injections. The relationship between the number of injections and all-cause mortality was investigated. Separate regression analyses were conducted to investigate this relationship in subgroups of studies with different diseases and drugs. RESULTS: Fifty-two trials were included. Overall mortality rates of 1.02% and 3.36% were recorded at 12 and 24 months, respectively. Univariate regression showed that a larger number of injections was not associated with a significant increase in mortality both at 12 months (IRR, 1.16; 95% CI, 0.87-1.53; P = 0.31) and at 24 months (IRR, 1.05; 95% CI, 0.95-1.15; P = 0.34). According to subgroup analyses, in diabetic macular edema (DME) studies, a higher risk was marginally associated with an increasing number of injections at 24 months (IRR, 1.17; 95% CI, 1.02-1.33; P = 0.03). CONCLUSION: No significant influence of anti-VEGF treatment intensity on mortality was shown, supporting a message of reassurance over safety concerns of this therapy. Marginal evidence of a higher risk associated with a more intense treatment was found in patients with DME.

Teprotumumab Efficacy, Safety, and Durability in Longer-Duration Thyroid Eye Disease and Re-treatment: OPTIC-X Study.

Douglas RS, Kahaly GJ, Ugradar S … +19 more , Elflein H, Ponto KA, Fowler BT, Dailey R, Harris GJ, Schiffman J, Tang R, Wester S, Jain AP, Marcocci C, Marinò M, Antonelli A, Eckstein A, Führer-Sakel D, Salvi M, Sile S, Francis-Sedlak M, Holt RJ, Smith TJ

Ophthalmology · 2022 Apr · PMID 34688699 · Publisher ↗

PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis wit... PURPOSE: To evaluate teprotumumab safety/efficacy in patients with thyroid eye disease (TED) who were nonresponsive or who experienced a disease flare. DESIGN: The Treatment of Graves' Orbitopathy to Reduce Proptosis with Teprotumumab Infusions in an Open-Label Clinical Extension Study (OPTIC-X) is a teprotumumab treatment and re-treatment trial following the placebo-controlled teprotumumab Phase 3 Treatment of Graves' Orbitopathy (Thyroid Eye Disease) to Reduce Proptosis with Teprotumumab Infusions in a Randomized, Placebo-Controlled, Clinical Study (OPTIC) trial. PARTICIPANTS: Patients who previously received placebo (n = 37) or teprotumumab (n = 14) in OPTIC. METHODS: OPTIC nonresponders or those who flared (≥2-mm increase in proptosis, ≥2-point increase in clinical activity score [CAS], or both) during follow-up were treated for the first time (previous placebo patients) or re-treated with teprotumumab in OPTIC-X with 8 infusions over 24 weeks. MAIN OUTCOME MEASURES: Proptosis response and safety. Secondary outcomes included proptosis, CAS, subjective diplopia, and quality-of-life. RESULTS: Thirty-three of 37 placebo-treated OPTIC patients (89.2%) became proptosis responders (mean ± standard deviation, -3.5 ± 1.7 mm) when treated with teprotumumab in OPTIC-X. The responses were equivalent to the OPTIC study. In these responders, proptosis, CAS of 0 or 1, and diplopia responses were maintained in 29 of 32 patients (90.6%), 20 of 21 patients (95.2%), and 12 of 14 patients (85.7%), respectively, at follow-up week 48. The median TED duration was 12.9 months versus 6.3 months in those treated with teprotumumab in the OPTIC study. Of the 5 OPTIC teprotumumab nonresponders re-treated in OPTIC-X, 2 responded, 1 showed a proptosis reduction of 1.5 mm from OPTIC baseline, and 2 discontinued treatment early. Of the OPTIC teprotumumab responders who experienced flare, 5 of 8 patients (62.5%) responded when re-treated (mean proptosis reduction, 1.9 ± 1.2 mm from OPTIC-X baseline and 3.3 ± 0.7 mm from OPTIC baseline). Compared with published double-masked trials and their integrated follow-up, no new safety signals were identified. Mild hearing impairment was reported; 4 events occurred during the first course of treatment, and 2 events reoccurred after re-treatment. CONCLUSIONS: Patients with TED of longer disease duration responded similarly to those treated earlier in the disease course. Patients with an insufficient initial response or flare may benefit from additional teprotumumab therapy. No new safety risk was identified; however additional postmarketing pharmacovigilance is ongoing.

Characteristics of retinal detachment associated with atopic dermatitis.

Lee Y, Park WK, Kim RY … +3 more , Kim M, Park YG, Park YH

BMC Ophthalmol · 2021 Oct · PMID 34635058 · Full text

BACKGROUND: To examine the characteristics of rhegmatous retinal detachment (RRD) associated with atopic dermatitis. METHOD: Medical records of 2257 patients who underwent RD surgery at this clinic between 2008 and 2018... BACKGROUND: To examine the characteristics of rhegmatous retinal detachment (RRD) associated with atopic dermatitis. METHOD: Medical records of 2257 patients who underwent RD surgery at this clinic between 2008 and 2018 were retrospectively reviewed. Among them, 61 patients who were diagnosed as AD were assigned into the experimental group and 100 patients who did not have AD were randomly selected and assigned into the control group. Demographics, characteristics of detachment, initial operative method, and prognosis after surgery were investigated as main outcomes. Additionally, in pseudophakic RD patients, the period between the cataract surgery and onset of RD was measured. RESULT: Postoperative VA and prognosis were significantly worse and bilateral involvement of RD was more common in the atopy group than in the control group. (P value = 0.005, 0.001 each) Characteristics of retinal breaks were different between the two groups. Additionally, the risk of developing RD within 1 year after cataract surgery was significantly higher in pseudophakic patients of the atopic group than in the control group. (P value = 0.013) However, there was no significant difference in mean preoperative VA or refractive index between the two groups. CONCLUSION: Our results show that in atopic patients, RD occurs at a young age with different characteristics compared to non-atopic patients. Atopic RD has a poor visual prognosis. Thus, it requires careful management. Furthermore, the risk of developing RD within 1 year after cataract surgery is higher in atopic patients. Therefore, it is important to perform regular and extensive check-up after cataract surgery for atopic patients.

Multimodal imaging of Hypotrichosis with juvenile macular dystrophy: a case report.

Carnovale-Scalzo G, Carnevali A, Piccoli G … +7 more , Ceravolo D, Bruzzichessi D, Iuliano R, Tallerico R, Gatti V, Giannaccare G, Scorcia V

BMC Ophthalmol · 2021 Jul · PMID 34301208 · Full text

BACKGROUND: To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging. CASE PRESENTATION: An 11-year-old boy was refe... BACKGROUND: To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging. CASE PRESENTATION: An 11-year-old boy was referred to our Institution for bilateral maculopathy of unknown origin. Multimodal imaging helps the diagnosis of Juvenile Macular Dystrophy with Hypotrichosis (HJMD). Fundus examination showed several alterations of the retinal pigment epithelium and circular pigmented area of chorioretinal atrophy. Structural spectral domain optical coherence tomography (OCT) showed some backscattering phenomenon with several alterations of retinal pigment epithelium and photoreceptor layer in both eyes. Moreover, OCT showed hyperreflective lesion beneath the neuroepithelium in left eye. OCT angiography (OCT-A) revealed a pathologic neovascular network in choriocapillaris plexus, probably the result of a fibrovascular membrane. Multifocal electroretinograms (MfERGs) showed functional alterations in 12.22° of the central retina. In order to confirm the suspicion of HJMD, the child and both parents underwent genetic testing. Both parents resulted to be heterozygous healthy carriers of a single variation. CONCLUSION: Multimodal imaging, in particular OCT-A, is a useful aid, along to clinical findings and genetics, for the diagnosis of inherited retinal dystrophies.

Iron overload and iron chelating agent exposure in anemia-associated outer retinal degeneration: a case report and review of the literature.

Belmouhand M, Eckmann-Hansen C, Ilginis T … +3 more , Leinøe EB, Mortensen BK, Larsen M

BMC Ophthalmol · 2021 Jul · PMID 34256738 · Full text

BACKGROUND: Deferoxamine retinopathy is the informally designated term used to describe a characteristic pattern of outer retinal degeneration in iron-overloaded chronic anemia patients who are treated with deferoxamine.... BACKGROUND: Deferoxamine retinopathy is the informally designated term used to describe a characteristic pattern of outer retinal degeneration in iron-overloaded chronic anemia patients who are treated with deferoxamine. We hypothesize that insufficiently treated iron overloading and not only deferoxamine is the cause of the retinal degeneration. Our case report is based on exposure histories of two anemia patients and literature review. CASE PRESENTATION: Both anemia patients presented with bilateral visual loss secondary to photoreceptor and retinal pigment epithelium degeneration. Chart review showed that visual loss came after a year-long slow, and rather monotonous rise in plasma ferritin concentrations, with no obvious relation to iron chelator exposure. In one patient, the onset of symptomatic visual loss came after a bout of fever followed by two additional febrile episodes, all accompanied by plasma ferritin spikes. Adjustment of iron chelation therapy did not improve visual function. Experimental studies clearly show that both systemic and intraocular exposure to iron ions can induce retinal degeneration. CONCLUSION: The available evidence indicates that retinal degeneration in chronic anemia patients treated by deferoxamine is cause by insufficient iron chelation, not by deferoxamine. The actual role of iron chelating agents may be to promote a long enough survival to allow the slow development of retinal siderosis.

A clinical decision model based on machine learning for ptosis.

Song X, Tong W, Lei C … +4 more , Huang J, Fan X, Zhai G, Zhou H

BMC Ophthalmol · 2021 Apr · PMID 33836706 · Full text

BACKGROUND: To establish a decision model based on two- (2D) and three-dimensional (3D) eye data of patients with ptosis for developing personalized surgery plans. METHODS: Data of this retrospective, case-control study... BACKGROUND: To establish a decision model based on two- (2D) and three-dimensional (3D) eye data of patients with ptosis for developing personalized surgery plans. METHODS: Data of this retrospective, case-control study was collected from March 2019 to June 2019 at the Department of Ophthalmology, Shanghai Ninth People's Hospital, and then the patients were followed up for 3 months. One hundred fifty-two complete feature eyes from 100 voluntary patients with ptosis and satisfactory surgical results were selected, with 48 eyes excluded due to any severe condition or improper collection and shooting angle. Three experimental schemes were set as follows: use 2D distance alone, use 3D distance alone, and use two distances at the same time. The five most common evaluation indicators used in the binary classification problem to test the decision model were accuracy (ACC), precision, recall, F1-score, and area under the curve (AUC). RESULTS: For diagnostic discrimination, recall of "3D", "2D" and "Both" schemes were 0.875, 0.875 and 0.938 respectively. And precision of the three schemes were 0.8333, 0.7778 and 1.0000 for the surgical procedure classification. Values of "Both" scheme that combined 2D and 3D data were the highest in two classifications. CONCLUSIONS: In this study, 3D eye data are introduced into clinical practice to construct a decision model for ptosis surgery. Our decision model presents exceptional prediction effect, especially when 2D and 3D data employed jointly.

Ocular and corneal aberrations changes in controlled randomized clinical trial MiSight® Assessment Study Spain (MASS).

Lopes-Ferreira D, Ruiz-Pomeda A, Peréz-Sanchéz B … +2 more , Queirós A, Villa-Collar C

BMC Ophthalmol · 2021 Mar · PMID 33648464 · Full text

BACKGROUND: To compare ocular and corneal inherent aberrations in the naked eyes of randomly selected children fitted with MiSight contact lenses (CL) for myopia control, versus children corrected with single-vision spec... BACKGROUND: To compare ocular and corneal inherent aberrations in the naked eyes of randomly selected children fitted with MiSight contact lenses (CL) for myopia control, versus children corrected with single-vision spectacles (control), over a 24-months period. METHODS: Children aged 8 to 12 years, with myopia (-0.75 to -4.00 D sphere) and astigmatism (< -1.00 D cylinder) were randomly assigned to the lens study group (MiSight) or the control group (single-vision spectacles). The root mean square aberration (RMS) was determined as corneal (RMS_C), corneal high order RMS (HO_RMS_C), corneal low order RMS (LO_RMS_C), ocular (total) RMS (RMS_T), ocular high order RMS (HO_RMS_T), ocular low order RMS (LO_RMS_T), corneal spherical aberration (SA_C) and ocular SA (SA_T) were calculated by aberrometry measures at the baseline, on 12-months and 24-months visits. A 5 mm diameter was defined for the analysis in all visits for all subjects. Only the dominant eye was analyzed. RESULTS: Seventy-four subjects completed the clinical trial: 41 subjects from the MiSight group (age: 11.01 ± 1.23 years) and 33 from the single-vision group (age: 10.12 ± 1.38 years). RMS_T significantly changed (0.57 ± 0.20 µm, p = 0.029) after 24-months in the control group. In the MiSight group no significant changes were registered (p > 0.05). The SA_C and SA_T did not reveal significant changes between visits or between groups (p > 0.05). CONCLUSIONS: Along 2 years, MiSight CL did not induce significant changes in RMS of anterior cornea or total ocular RMS. Contrary, in control group the RMS_T significantly changed as response of greater eye growth and myopia progression. The results obtained in present study allow to predict corneal or total aberration changes, in children, in response of wearing of MiSight lens along the time. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01917110.

Glaucoma and Computer Use: Do Contrast and Color Enhancements Improve Visual Comfort in Patients?

Garric C, Rouland JF, Lenoble Q

Ophthalmol Glaucoma · 2021 · PMID 33556588 · Publisher ↗

PURPOSE: To estimate the impact of glaucoma on computer use and to assess specific adaptations of the graphical interface to this form of visual impairment. DESIGN: Prospective, experimental cohort study. PARTICIPANTS: F... PURPOSE: To estimate the impact of glaucoma on computer use and to assess specific adaptations of the graphical interface to this form of visual impairment. DESIGN: Prospective, experimental cohort study. PARTICIPANTS: Forty-nine participants were recruited: 16 patients with primary open-angle glaucoma (mean ± SD, 62.7 ± 5.6 years of age), 17 age-matched participants (mean ± SD, 59.1 ± 8.3 years of age), and 16 young control participants (mean ± SD, 23.3 ± 2.1 years of age). METHODS: An ophthalmologic examination before the study evaluated the level of visual loss (mean deviation), visual acuity (logarithm of the minimum angle of resolution units), and contrast sensitivity (CS) of the primary open-angle glaucoma patients. Each participant underwent the following measurements: an information technology (IT) experience questionnaire, a preference task monitored by eye tracking, and a feedback session. The experimental task was based on ecological computer scenes with 3 enhancement levels (low, medium, and high), determined by gradual modulation of contrast, luminance, and color. Participants were asked to select the most readable and comfortable stimulus among 4 images displayed on the screen: the original computer scene and 3 enhanced versions. MAIN OUTCOME MEASURES: Clinical, oculomotor, and subjective data were computed together in a multivariate model by using a principal component analysis (PCA). RESULTS: The PCA revealed 3 principal components accounting for 72% of the total variance of the data and showed a greater need for enhanced computer scenes in glaucoma patients, an equal preference for low and medium enhancement within the 3 groups, and significantly longer oculomotor behavior in the patient groups. Subjective reports of difficulty using IT because of vision were correlated with visual impairment and high enhancement preference. Contrast sensitivity was critical to explaining the main variations of the data. A reduced CS had a significant effect on the preference for enhanced computer scenes (r = -0.43; P < 0.002) and a less effective exploration velocity (r = 0.43; P < 0.002). CONCLUSIONS: Glaucoma alters the global exploration of computer scenes. High enhancement of the graphical interface could improve visual comfort during computer use. Subjective patients' reports underline the importance of including IT questions in visual-related quality-of-life questionnaires.

X-linked dominant RPGR gene mutation in a familial Coats angiomatosis.

Nebbioso M, Franzone F, Lambiase A … +4 more , La Cava M, Mallone F, Pizzuti A, Marchionni E

BMC Ophthalmol · 2021 Jan · PMID 33446141 · Full text

BACKGROUND: Retinitis Pigmentosa (RP) is the most frequent retinal hereditary disease and every kind of transmission pattern has been described. The genetic etiology of RP is extremely heterogeneous and in the last few y... BACKGROUND: Retinitis Pigmentosa (RP) is the most frequent retinal hereditary disease and every kind of transmission pattern has been described. The genetic etiology of RP is extremely heterogeneous and in the last few years the large application of Next Generation Sequencing (NGS) approaches improved the diagnostic yield, elucidating previously unexplained RP causes and new genotype-phenotype correlations. The objective of this study was to reevaluate a previously reported family affected by Coats'-type RP without genetic diagnosis and to describe the new genetic findings. CASE PRESENTATION: Cohort, prospective, and single-center observational family case. Three individuals of a family, consisting of a mother and four sons, with a Coats phenotype were revaluated after 25 years of clinical follow-up using visual acuity tests, ophthalmoscopy, Goldmann visual field, electroretinography (ERG), and spectral domain-optical coherence tomography (SD-OCT). Specifically, a RP NGS panel was performed on one member of the family and segregation analysis was required for the other affected and unaffected members. NGS analysis disclosed a RPGR (Retinitis Pigmentosa GTPase Regulator) gene truncating variant segregating with the phenotype in all the three affected members. RPGR mutations are reported as causative of an X-linked RP. CONCLUSIONS: This is the first reported family with a Coats'-type RP associated to a RPGR mutation and segregating as a dominant X-linked disease, confirming the hypothesis of the genetic origin of this condition and expanding the phenotypic spectrum of diseases caused by RPGR gene mutations. The Authors suggest RPGR gene screening mutations in patients presenting this phenotype.

Effects of Lidocaine on Mitomycin C Cytotoxicity.

Park A, Hardin JS, Bora NS … +1 more , Morshedi RG

Ophthalmol Glaucoma · 2021 · PMID 33080409 · Publisher ↗

PURPOSE: Intra-Tenon or subconjunctival injection of a solution of mitomycin C (MMC) and 1% preservative-free lidocaine (as an anesthetic) has gained popularity for its use in trabeculectomy, a filtering surgery for glau... PURPOSE: Intra-Tenon or subconjunctival injection of a solution of mitomycin C (MMC) and 1% preservative-free lidocaine (as an anesthetic) has gained popularity for its use in trabeculectomy, a filtering surgery for glaucoma. To our knowledge, no studies have analyzed the impact of lidocaine on the cytotoxic effects of MMC in this setting. This study was conducted to evaluate in vitro fibroblast cytotoxicity to a solution of MMC (0.2 mg/ml) and 1% preservative-free lidocaine. DESIGN: Experimental study. PARTICIPANTS: Nonhuman subject research. METHODS: Cultured human conjunctival fibroblasts were incubated in phosphate-buffered saline (PBS) (control), MMC (0.2 mg/ml), a mixture of 0.2 mg/ml MMC + 1% preservative-free lidocaine, or 1% preservative-free lidocaine. Samples were taken at 2, 5, 10, 30, and 60 minutes, and a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay with photoabsorbance testing was used to assess conjunctival cell viability. MAIN OUTCOME MEASURE: Mean photoabsorbance. RESULTS: Mean photoabsorbance across all time intervals was 0.680 for solutions incubated in PBS, 0.642 for MMC, 0.612 for MMC + 1% preservative-free lidocaine, and 0.605 for 1% preservative-free lidocaine. A 2-way analysis of variance analyzing solution, time, and solution-time interaction on photoabsorbance showed that PBS was least cytotoxic and an optimal control for this study. Tukey post hoc comparisons showed that MMC was more cytotoxic than PBS (P < 0.001). However, both MMC + 1% preservative-free lidocaine and 1% preservative-free lidocaine were more cytotoxic than MMC and PBS (P < 0.01 for all). No significant differences in cytotoxicity comparing lidocaine-containing solutions were observed. CONCLUSIONS: In this in vitro study, we found an increase in cytotoxicity when MMC (0.2 mg/ml) was combined with 1% preservative-free lidocaine. We note that lidocaine did not inhibit MMC cytotoxicity and exhibited a significant cytotoxic effect on its own.

Multi-parametric evaluation of autologous cultivated Limbal epithelial cell transplantation outcomes of Limbal stem cell deficiency due to chemical burn.

Selver OB, Gurdal M, Yagci A … +8 more , Egrilmez S, Palamar M, Cavusoglu T, Veral A, Guven C, Ates U, Wang Z, Wolosin JM

BMC Ophthalmol · 2020 Aug · PMID 32762738 · Full text

BACKGROUND: The sparsity of established tools for the grading of limbal stem cell deficiency hinder objective assessments of the clinical outcome of cultivated limbal epithelial cell transplantation. To advance towards t... BACKGROUND: The sparsity of established tools for the grading of limbal stem cell deficiency hinder objective assessments of the clinical outcome of cultivated limbal epithelial cell transplantation. To advance towards the development of standards for the comparison of the outcomes of these bio-surgical protocols we have now applied a battery of recognized objective and patient-declared subjective outcome criteria to the autologous modality of cultivated limbal epithelial cell transplantation. METHODS: The prospective study involved ten patients (M/F = 9/1; mean age = 42.1 years) displaying overt unilateral limbal stem cell deficiency complying with the inclusion criteria described in Methods. Limbal biopsies were obtained from the contralateral eye and their outgrowths after 2-week cultures were transplanted on the affected eye after pannus resection. Outcomes were followed up for 12 months. The objective tests were scores for best-corrected visual acuity (BCVA); using the LogMAR scale, a multiparametric ocular surface score (OSS), and the Schirmer's test. Subjective scores were based on patient answers to a) perception of visual improvement/pain; b) the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ 25); and c) the 12-item Ocular Surface Disease Index Questionnaire (OSDI). All procedures were performed under good manufacture practices using solely xeno-free reagents. In all cases, a single biopsy was divided into two pieces and they were expanded in order to prevent outgrowth failure. In 5 patients, both biopsies generated healthy culture sheet. In those cases the lesser outgrowth were used for immune-histological characterization. RESULTS: The experimental parallel outgrowth samples showed a similar percent of p63α cells. PreOp and 12-month PostOp BCVAs and OSSs were, respectively, 1.15 ± 0.70; 0.21 ± 0.13 and 7.40 ± 2.01; 2,30 ± 1.30, (p < 0.05). Patient's responses to all three question sets except ocular pain were consistent with significant improvement (p < 0.05). CONCLUSION: Objective clinical metrics demonstrate that in patients with limbal stem cell deficiency, cultivated limbal epithelial cell transplantation improves vision and ocular surface health and subjective visual perceptions.
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