Intraocular cetuximab: Safety and effect on axial elongation in young Guinea pigs with lens-induced myopization.

This study aimed to examine the intraocular tolerability of the epidermal growth factor receptor antibody cetuximab, when applied intravitreally, and its effect on axial elongation. Guinea pigs aged 2-3 weeks were subjected to bilateral plano glasses and bilateral lens-induced myopization (LIM) as a single procedure for group I (n = 8) and group II (n = 8), respectively. In the animals of group III (n = 8), group IV (n = 8), and group V (n = 8), the right eyes of the animals, in addition to LIM, received four weekly intravitreal injections of cetuximab (Erbitux®) in doses of 6.25 µg, 12.5 µg, and 25 µg, respectively. As controls, the left eyes, in addition to LIM, received corresponding intraocular injections of phosphate-buffered saline. The animals underwent regular ophthalmoscopic examinations and biometry for axial length measurements. With increasing doses of cetuximab, the inter-eye difference in axial elongation (at study end, left eyes minus right eyes) were significantly the smallest in group I (0.00 ± 0.02 mm) and group II (-0.01 ± 0.02 mm), they were larger in group III (0.04 ± 0.04 mm) and group IV (0.10 ± 0.03 mm), and they were the largest in group V (0.11 ± 0.01 mm). The inter-eye difference in axial elongation enlarged (P < 0.001) with the number of injections applied. Retinal thickness at the posterior pole (right eyes) was significantly thicker in group V than in group II (P < 0.01). The density of apoptotic cells (visualized by TUNEL-staining) did not vary significantly between any of the groups (all P > 0.05). The results suggest that intravitreal injections of cetuximab in young guinea pigs with LIM resulted in a reduction in axial elongation in a dose-dependent and number of treatment-dependent manner. Intraocular toxic effects, such as intraocular inflammation, retinal thinning, or an increased density of apoptotic cells in the retina, were not observed in association with the intravitreally applied cetuximab.

Association between weight-adjusted waist index and myopia in adolescents and young adults: results from NHANES 1999-2008.

BACKGROUND: Previous studies have indicated a possible link between obesity and myopia, although the results have varied. The objective of this study was to investigate the correlation between a new measure of obesity, the weight-adjusted waist index (WWI), and myopia. METHOD: This cross-sectional study included individuals between the ages of 12 and 25 who participated in a noncycloplegic vision examination as part of the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2008. WWI was calculated as waist circumference divided by the square root of body weight. Myopia was characterized by a spherical equivalent (SE) of ≤ - 0.5 diopters (D) and further categorized into mild (-3.00D < SE≤-0.50 D), moderate (-6.00D < SE ≤-3.00 D), or high (SE≤-6.00 D). We utilized a weighted multivariable logistic regression and a generalized additive model to evaluate the correlation between WWI and myopia. Threshold effects were analyzed, and we performed subgroup analysis and interaction tests. RESULTS: A grand total of 11,180 individuals were registered for the study. Decreased myopia severity was observed with higher WWI, as evidenced by elevated SE (ß = 0.098, 95% CI: 0.028-0.167). Individuals in the top tertile of WWI experienced a 19.8% decrease in risk compared to those in the lowest group (OR = 0.802, 95% CI: 0.800-0.804; P for trend < 0.001). Similar associations were observed for high myopia. Gender-specific nonlinear associations were found, with different breakpoints for males (10.774) and females (10.025). In males, a significant positive association was found on the right side of the breakpoint (OR = 1.398, 95% CI: 1.038-1.884), while no significant association was found on the left side. Conversely, among females, a negative association was observed on the left side of the breakpoint (OR = 0.679, 95% CI: 0.512-0.899), whereas no notable correlation was detected on the right side. CONCLUSION: Increased WWI level was linked to a lower risk of myopia and high myopia in the overall sample, with gender-specific variations.

Lens-induced myopization and body weight in young guinea pigs.

BACKGROUND: To investigate the relationship between body weight and Axial length in guinea pigs. METHODS: Forty pigmented guinea pigs were randomly divided into two groups, namely control group and negative lens-induced myopization (LIM) group. After measuring the baseline axial length and body weight (BW), guinea pigs of LIM group received bilateral negative lens-induced myopization using - 10.0 diopters lenses. One week later, the lenses were removed and biometric and ophthalmoscopic examinations were repeated. RESULTS: Two groups of guinea pigs showed no statistical difference in initial body weight and eye axis length. Compared to the control group, the lens-induced group had a lower weight (P = 0.02) and a longer axial length (P < 0.01) at the end of study Neither at baseline nor at week 1 did AL correlate with BW in both groups (Control Baseline: r = 0.306, P = 0.19; Control Week1: r = 0.333, P = 0.15; LIM Baseline: r=-0.142, P = 0.55; LIM Week 1: r = 0.189, P = 0.42). Lens-induction had a significant effect on axial elongation (P < 0.01) while body weight had no impact on such aspect (P > 0.05). CONCLUSION: In guinea pigs of the same age, axial length was not correlated with body weight. Also, baseline body weight had no impact on natural axial length growth or lens-induced myopia. Lens-induction caused a significant reduction in body weight gain.

Vitamin D and myopia: a review.

Myopia is a worldwide public health problem of vision disorder caused by multiple factors, which has posed a huge socioeconomic burden, raising concerns about sight-threatening ocular complications. Vitamin D, as a kind of fat-soluble vitamin, related to time-spent-outdoors, has been considered by extensive studies to have potential relationship with myopia. We reviewed studies published in a decade which estimated the association of blood vitamin D status with myopia and summarized the universality and individuality of all research articles. Several research articles suggested the known environmental risk factors of myopia, including age, gender, ethnicity, education level, parental and school conditions, time-spent-outdoors, and sunlight exposure, and recent epidemiological studies demonstrate that increased vitamin D levels, by virtue of the extended outdoor time, may be an important modifiable factor and a protective effect that delay the progression of myopia in children and adolescents rather than in adults. The genetic studies have been conducted to get access to the evidence of gene polymorphism for explaining the association of serum vitamin D status and myopia, but the precise genetic interpretation of vitamin D and myopia remains unclear so far; on the other hand, the possible mechanisms are various like copolymerization mechanism, calcium homeostasis and imbalance of ciliary muscle function regulation, but nearly all of the investigators are inclined to remain skeptical. This article reviews the age-related epidemiological proofs, existent genetics correlations, possible underlying biological mechanisms and further values for the protective association between vitamin D and myopia, providing the possibility of prevention or postponement for myopia.

Development and validation of medical record-based logistic regression and machine learning models to diagnose diabetic retinopathy.

PURPOSES: Many factors were reported to be associated with diabetic retinopathy (DR); however, their contributions remained unclear. We aimed to evaluate the prognostic and diagnostic accuracy of logistic regression and three machine learning models based on various medical records. METHODS: This was a cross-sectional study. We investigated the prevalence and associations of DR among 757 participants aged 40 years or older in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). We trained the models to predict if the participants had DR with 15 predictor variables. Area under the receiver operating characteristic (AUROC) and mean squared error (MSE) of each algorithm were compared in the external validation dataset using a replicate cohort from NHANES 2007-2008. RESULTS: Among the 757 participants, 53 (7.00%) subjects had DR, the mean (standard deviation, SD) age was 57.7 (13.04), and 78.0% were male (n = 42). Logistic regression revealed that female gender (OR = 4.130, 95% CI: 1.820-9.380; P < 0.05), HbA1c (OR = 1.665, 95% CI: 1.197-2.317; P < 0.05), serum creatine level (OR = 2.952, 95% CI: 1.274-6.851; P < 0.05), and eGFR level (OR = 1.009, 95% CI: 1.000-1.014, P < 0.05) increased the risk of DR. The average performance obtained from internal validation was similar in all models (AUROC ≥ 0.945), and k-nearest neighbors (KNN) had the highest value with an AUROC of 0.984. In external validation, they remained robust or with modest reductions in discrimination with AUROC still ≥ 0.902, and KNN also performed the best with an AUROC of 0.982. Both logistic regression and machine learning models had good performance in the clinical diagnosis of DR. CONCLUSIONS: This study highlights the utility of comparing traditional logistic regression to machine learning models. We found that logistic regression performed as well as optimized machine learning methods when classifying DR patients.

Prevalence and associated health and lifestyle factors of myopic maculopathy in northern China: the Kailuan eye study.

BACKGROUND: To evaluate the prevalence and associated health and lifestyle factors of myopic maculopathy (MM) in a northern Chinese industrial city. METHODS: The cross-sectional Kailuan Eye Study included subjects who participated in the longitudinal Kailuan Study in 2016. Ophthalmologic and general examinations were performed on all the participants. MM was graded based on fundus photographs using the International Photographic Classification and Grading System. The prevalence of MM was evaluated. Univariate and multiple logistic regression were adopted to evaluated risk factors of MM. RESULTS: The study included 8330 participants with gradable fundus photographs for MM and ocular biometry data. The prevalence of MM was 1.11% (93/8330; 95% confidence interval [CI] 0.89-1.33%). Diffuse chorioretinal atrophy, patchy chorioretinal atrophy, macular atrophy, and plus lesions were observed in 72 (0.9%), 15 (0.2%), 6 (0.007%), and 32 eyes (0.4%), respectively. MM was more common in eyes with longer axial length (OR 4.517; 95%CI 3.273 to 6.235) and in participants with hypertension (OR 3.460; 95%CI 1.152 to 10.391), and older age (OR 1.084; 95%CI 1.036 to 1.134). CONCLUSIONS: The MM was present in 1.11% of the northern Chinese individuals 21 years or older and the associate factors include longer axial length, older age, and hypertension.

Clinical Analysis of Primary Malignant Lacrimal Sac Tumors: A Case Series Study With a Comparison to the Previously Published Literature.

PURPOSE: To report management of a series of patients with primary malignant lacrimal sac tumors and to compare these results to the previously published literature. MATERIALS AND METHODS: A total of 27 patients with pathologically confirmed primary malignant lacrimal sac lesions were enrolled into this study. Pathological classifications, clinical characteristics, various treatment modalities and follow-up time, including tumor recurrence, were documented. The outcome measures included overall survival, progression-free survival, and median survival time. RESULTS: Among 27 eligible cases, 33.33% (9/27) of the tumor was non-Hodgkin B-cell lymphoma, and 33.33% (9/27) was squamous cell carcinoma; both were the most common tumor in this series, followed by adenocarcinoma 18.52% (5/27), then melanoma 7.41% (2/27). Treatment modalities included surgery, radiotherapy, and/or chemotherapy, the overall survival rate of 27 patients was 70.37%, with a median follow-up of 45 months (range: 7 mo-16 y), 8 patients had died from metastatic disease, but 13 patients remained without evidence of recurrent tumor. The 5-year overall survival and progression-free survival for all cases were 73.33% and 66.67%, respectively. The median survival time for 5 deceased patients with interstitial brachytherapy was 98 months, and 5-year survival rate was 60%. CONCLUSIONS: In this series, among primary malignant lacrimal sac tumors, the proportion of lymphoma had increased when compared with the previously published literature, and multidisciplinary therapy may lead to a good prognosis in the majority of patients with the tumors and patients may benefit more from interstitial brachytherapy than external beam radiotherapy.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022).

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Whole-exome sequencing identified genes known to be responsible for retinitis pigmentosa in 28 Chinese families.

Purpose: Retinitis pigmentosa (RP) is a group of highly heterogenetic inherited retinal degeneration diseases. Molecular genetic diagnosis of RP is quite challenging because of the complicated disease-causing mutation spectrum. The aim of this study was to explore the mutation spectrum in Chinese RP patients using next-generation sequencing technology and to explore the genotype-phenotype relationship. Method: In this study, a cost-effective strategy using whole-exome sequencing (WES) was employed to address the genetic diagnosis of 28 RP families in China. One to two patients and zero to two healthy relatives were sequenced in each family. All mutations in WES data that passed through the filtering procedure were searched in relation to 662 gene defects that can cause vision-associated phenotypes (including 89 RP genes in the RetNet Database). All patients visiting the outpatient department received comprehensive ophthalmic examinations. Result: Twenty-five putative pathogenic mutations of 12 genes were detected by WES and were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including the 12 following genes: USH2A, CYP4V2, PRPF31, RHO, RP1, CNGA1, CNGB1, EYS, PRPF3, RP2, RPGR, and TOPORS. Three families were rediagnosed as having Bietti crystalline dystrophy (BCD). USH2A (4/20, 20%) and CYP4V2 (3/20, 15%) were found to be the most frequent mutated genes. Seven novel mutations were identified in this research, including mutations in USH2A1, USH2A2, PRPF31, RP2, TOPORS, CNGB1, and RPGR. Phenotype and genotype relationships in the 12 RP genes were analyzed, which revealed later disease onset and more severe visual function defects in CYP4V2. Conclusion: Twenty-five putative pathogenic mutations of 12 genes were detected by WES, and these were all confirmed by Sanger sequencing in 20 (20/28, 71.4%) families, including seven novel mutations. USH2A and CYP4V2 were found to be the most frequent genes in this research. Phenotype and genotype relationships were revealed, and the mutation spectrum of RP in Chinese populations was expanded in this research, which may benefit future cutting-edge therapies.

Progression and associated factors of lacquer cracks/patchy atrophies in high myopia: the Beijing Eye Study 2001-2011.

PURPOSE: To assess the development and progression of lacquer cracks/patchy atrophies (LCs/PAs) in high myopia. METHODS: The case control study included highly myopic eyes (refractive error ≤ - 6.0 diopters), examined in the population-based Beijing Eye Study 2001/2011. Using fundus photographs taken in 2001 and 2011 and optical coherence tomographic images obtained in 2011, we assessed the incidence and enlargement of pre-existing LC/PAs. RESULTS: The study included 89 highly myopic eyes (age: 65.0 ± 9.4 years). Newly developed or enlarged LC/PAs were detected in 17 (19.1%; 95% confidence interval (CI): 11.0, 27.0) eyes, with a new LC development without previous LCs, enlargement of a pre-existing LC, LC enlargement to a PA, development of a new PA without any previous LCs, and enlargement of a pre-existing PA detected in 3, 3, 5, 3, and 3 eyes, respectively. In 14 (82.4%; 95%CI: 62.3, 100) of the 17 eyes with LC/PA development or enlargement, the LC/PAs elongated perpendicularly to, and widened in, the direction of gamma zone enlargement. Higher prevalence of LC/PA enlargement was associated (multivariable analysis) with higher myopic maculopathy stage in 2001 (odds ratio (OR): 7.83; 95%CI: 2.65, 23.2; P < 0.001) and higher frequency of parapapillary delta zone enlargement (OR: 32.0; 95%CI: 3.07, 334; P < 0.001). Prevalence of LC/PA enlargement was lower than the prevalence of changes in other myopic maculopathy features (disc-fovea distance elongation: 71%; choroidal vessel shift: 55%; reduction in ophthalmoscopical disc size: 34%; ophthalmoscopic disc size enlargement: 25%). All eyes with LC/PA enlargement showed a pre-existing and enlarging gamma zone. CONCLUSIONS: Development and enlargement of LC/PAs were associated with enlargement of parapapillary delta zone and often occurred in association with the direction of gamma zone enlargement.

Beta zone parapapillary atrophy in elderly Chinese.

PURPOSE: Assess the beta zone parapapillary atrophy in elderly Chinese. PATIENTS AND METHODS: The Beijing Eye Study 2011 is a population-based cross-sectional study, which includes 3468 patients with the average age of 64.5 ± 9.8 years. The beta zone of parapapillary atrophy was captured and analyzed morphometrically by using colour optic disc photographs. RESULTS: The beta zone was found in 1358 (39.9%) eyes, measuring 0.37 ± 0.84 mm2 in size, 203.5 ± 81.8° in circumferential angle, 0.36 ± 0.27 mm in the maximum radial extent, the most often and longest in the temporal peripapillary region, followed by the temporal inferior region and the temporal superior region, the nasal region at least. Beta zone has statistically significant association with male gender (P = 0.001), myopic refractive error (P = 0.003), thinner retinal nerve fiber layer thickness (P<0.001), thinner subfoveal choroidal thickness (P<0.001), bigger size of optic disc size (P<0.001). The size of beta zone has statistically significant association with longer axial length (P = 0.004)，increasing age (P<0.001), urban (P = 0.025), cardiovascular disease history (P = 0.025), with age related macular degeneration (P = 0.038), myopic ametropia (P<0.001), thinner retinal nerve fiber layer thickness (P = 0.001), thinner subfoveal choroidal thickness (P<0.001), bigger size of optic disc size (P = 0.001). CONCLUSION: The population prevalence of beta zone was 39.9% in elderly Chinese. The area of the beta zone has statistically significant association with age, urban, the thickness of retinal nerve fiber layer, age related macular degeneration, cardiovascular disease history, axial length, myopic refractive error, size of optic disc size, the thickness of subfoveal choroid.

Prevalence and associations of asteroid hyalosis: the Beijing Eye Study.

BACKGROUND: To determine the prevalence and associations of asteroid hyalosis (AH) in a Chinese population-based cohort. METHODS: The retrospective, cross-sectional, population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6 ± 9.8 years (range: 50-93 years). Participants underwent detailed ophthalmic examinations including fundus photographs for diagnosis of AH. Data on systemic and ocular factors were collected for all participants according to the standardized protocol. Multiple linear regression and multivariate Logistic regression analysis were performed. RESULTS: Fundus photographs were gradable in 3419 subjects. AH was detected in 63 (0.9%, 95% CI: 0.7%, 1.1%) eyes of 53 (1.6%, 95% CI: 1.1%, 2.0%) subjects. AH was bilateral in 18.9%. Mean age of all subjects with AH was 69.2 ± 9.5 years (median, 71.0 years; range, 51-91 years), mean spherical equivalent was 0.63 ± 1.53D (median, 0.75 D; range, -4.12 to 4.00D). In multivariate analysis, prevalence of AH was associated with elder age (P = 0.014, OR 1.057), thicker lens (P = 0.032, OR 3.887), higher spherical equivalent (P = 0.017, OR 1.396). CONCLUSIONS: In adult Chinese in Beijing, the prevalence of AH was 0.9% for eyes or 1.6% for subjects. AH was associated with elder age, thicker lens, and higher spherical equivalent. It was not associated with diabetes or other systemic indicators.

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

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.

[A monoclonal antibody-based icELISA for puerarin].

Puerarin was conjugated with bovine serum albumin(BSA) and ovalbumin(OVA) by periodate oxidation to serve as the immunogen and coating antigen, respectively. BALB/c mice were immunized with puerarin-BSA according to the routine immunization procedure, and the titer and specificity of serum were detected after three immunization. After booster immunization, mouse spleen lymphocytes were fused with mouse myeloma cells, and 24 hybridoma cell lines of the monoclonal antibodies against puerarin were screened by monoclonal antibody screening technique. Ascites was prepared and purified. The cross-reactivity of monoclonal antibody(mAb) M1 with 4'-methoxy puerarin, daidzin, puerarin-6″-O-xyloside, daidzein, mirificin, 3'-methoxy puerarin, and 3'-hydroxy puerarin was 239.84%, 112.18%, 67.89%, 58.28%, 22.37%, 0.40%, and 0.20%, respectively, and those with other analogs such as baicalein and baicalin were all less than 0.10%. The IC_(50) and the working range of the indirect competitive enzyme-linked immunosorbent assay(icELISA) for puerarin were 44.80 ng·mL~(-1) and 8.20-292.30 ng·mL~(-1), respectively. The average recovery was 91.95%-98.20% with an RSD in the range of 0.70%-2.60%. The content of puerarin in different Puerariae Lobatae Radix samples was determined with icELISA and validated by UPLC-MS. The correlation between data obtained from icELISA and UPLC-MS was 0.999 0, indicating that icELISA is suitable for the rapid detection of puerarin in Puerariae Lobatae Radix samples.

Blockade of epidermal growth factor and its receptor and axial elongation in experimental myopia.

To examine the influence of epidermal growth factor (EGF) and its receptor (EGFR) on axial ocular elongation, we intraocularly injected an EGF antibody and an EGFR antibody into young guinea pigs with lens-induced axial elongation (myopization). Mean axial elongation was reduced in the eyes injected with the EGF/EGFR-antibody compared with the contralateral control eyes injected with PBS (phosphate-buffered solution) (0.43 ± 0.13 mm vs 0.53 ± 0.13 mm; P < .001). The intereye difference in axial length increased (P = .005) as the doses of the EGF antibody and EGFR antibody increased. As a corollary, the thickness of the retina at the posterior pole was dose-dependently increased in the injected eyes compared to the contralateral control eyes. Immunohistochemical staining for EGF and the relative mRNA expression of EGF and EGFR were the highest in eyes not injected with the EGF antibody or EGFR antibody and decreased (P < .05) as the dose of EGF antibody or EGFR antibody increased. In an in vitro study, EGF had a stimulating effect and the EGF antibody had an inhibitory effect on the proliferation and migration of RPE cells. The findings showed that the intravitreal application of an EGF antibody and EGFR antibody is associated with a dose-dependent reduction in lens-induced axial elongation in young guinea pigs. The EGFR family may play a role in axial elongation of the eye and in the development of myopia.

RETINAL MICROVASCULAR CHANGES IN UVEAL MELANOMA FOLLOWING CONBERCEPT INJECTION AFTER PLAQUE RADIOTHERAPY AS DETECTED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To investigate macular microvascular characteristics imaged by optical coherence tomography angiography in patients with uveal melanoma following conbercept injections after plaque radiotherapy. METHODS: Prospective comparative analysis comprising 15 patients with uveal melanoma with conbercept injections and 30 patients without conbercept injections after plaque radiotherapy by optical coherence tomography angiography. The conbercept group received intravitreal conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal conbercept injection. RESULTS: After initiation of conbercept injections, superficial retinal vascular density in the whole image and parafoveal region were significantly higher at 6 months, whereas there was no significant difference at 9 months and 12 months. In analysis of variance analysis, superficial retinal vascular density in the whole image remained stable after conbercept injections (P = 0.069), whereas the superficial retinal vascular density decreased significantly after plaque radiotherapy in the control group (P = 0.011). In multivariable linear regression, a higher superficial retinal vascular density in the whole image region at 6 months was significantly associated with intravitreal conbercept injection (P = 0.018), wider tumor base (P = 0.026), and thinner tumor thickness (P = 0.04). CONCLUSION: Optical coherence tomography angiography can provide a quantitative evaluation of early retinal microvascular changes after radiotherapy. Intravitreal conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma; however, it may not be able to provide long-term positive functional outcomes.

Regression patterns of uveal melanoma after iodine-125 plaque brachytherapy.

BACKGROUND: Tumor regression of uveal melanomas (UMs) after radiotherapy has been reported as a valuable prognostic factor for metastasis and metastatic death. But its effect on prognosis is questionable. The purpose of this study was to summarize the regression features of uveal melanoma after iodine-125 plaque brachytherapy and the relationship with prognosis. METHODS: Adult uveal melanoma patients who only received iodine-125 plaque brachytherapy between December 2009 and March 2018 at the Beijing Tongren Hospital, Capital Medical University were enrolled in this study. The regression rate was calculated as the percent change in tumor height, and each eye was classified for four main regression patterns: Decrease (D), Stable (S), Others (O), and Increase (I), according to the trend of height change. Statistical analysis was performed using one-way ANOVA and chi-square test, univariate and multivariate logistic regression, and Kaplan-Meier analysis. RESULTS: A total of 139 patients was included in the study. The median follow-up was 35 months. Regression patterns status was pattern D in 65 tumors (46.8%), pattern S in 50 tumors (36.0%), pattern O in 6 tumors (4.3%), and pattern I in 18 tumors (12.9%). Reductions of tumor mean height for each follow-up visit were 5.26% (3 months), 10.66% (6 months), 9.37% (12 months), and 14.68% (18 months). A comparison (D vs. S vs. O vs. I) revealed the preoperative height of pattern I was significantly lower than the pattern D, S and O (mean: 7.24 vs. 7.30 vs. 6.77 vs. 5.09 mm, respectively; P = 0.037). LBD (largest basal diameter) was strongly associated with the metastasis (P = 0.03). However, an association between the tumor regression and subsequent melanoma-related metastasis and mortality could not be confirmed (P = 0.66 and P = 0.27, respectively). The tumor regression rate increased with increasing tumor height (P = 0.04) and decreased with increasing of LBD (P = 0.01). CONCLUSION: Our study showed a lack of association between the prognosis and the regression of uveal melanomas following I-125 plaque radiotherapy. The LBD and original height of the tumor have predictive value in tumor regression rate, and LBD was positively associated with metastasis.

Global, regional, and national prevalence, disability adjusted life years, and time trends for refraction disorders, 1990-2019: findings from the global burden of disease study 2019.

BACKGROUND: To evaluate global burden of refraction disorders by year, age, region, gender, socioeconomic status and other national characteristics in terms of disability adjusted life years (DALYs) and prevalence from Global Burden of Disease (GBD) study 2019 and World Bank Open Data 2019. METHODS: Global, regional, and national DALY numbers, crude DALY rates, age-standardized DALY and prevalence rates of refraction disorders were acquired from the GBD study 2019. Mobile cellular subscriptions, urban population, GDP per capita, access to electricity and total fertility rate were obtained from the World Bank to explore the factors that influenced the health burden of refraction disorders. Kruskal-Wallis test, linear regression and multiple linear regression were performed to evaluate the associations between the health burden with socioeconomic levels and other national characteristics. Wilcoxon Signed-Rank Test was used to investigate the gender disparity. RESULTS: Globally, age-standardized DALY rates of refraction disorders decreased from 88.9 (95% UI: 60.5-120.3) in 1990 to 81.5 (95% UI: 55.0-114.8) in 2019, and might fall to 73.16 (95% UI: 67.81-78.51) by 2050. Age-standardized prevalence rates would also reduce to 1830 (95% UI: 1700-1960) by 2050, from 2080 (95% UI: 1870-2310) in 1990 to 1960 (95% UI: 1750-2180) in 2019. In low SDI region, age-standardized DALY rates (equation: Y = 114.05*X + 27.88) and prevalence rates (equation: Y = 3171.1*X + 403.2) were positively correlated with SDI in linear regression respectively. East Asia had the highest blindness rate caused by refraction disorders in terms of age-standardized DALY rates (11.20, 95% UI: 7.38-16.36). Gender inequality was found among different age groups and SDI regions. CONCLUSION: Health burden of refraction disorders decreased in recent years, and may continue to alleviate in the next three decades. Older ages, females and lower socioeconomic status were associated with higher refraction disorders health burden.

Utility of Ultra-Wide-Field Imaging for Screening of AIDS-Related Cytomegalovirus Retinitis.

PURPOSE: To explore the potential use of ultra-wide-field (UWF) imaging for screening of cytomegalovirus retinitis (CMVR) in AIDS patients. METHODS: Ninety-four patients whose CD4 count was below 200 cells/µL were enrolled in a prospective study. Each patient underwent UWF imaging and indirect ophthalmoscopy. The main outcome measures were the concordance and detection rates of these 2 approaches and the sensitivity and specificity of UWF imaging. RESULTS: Twenty-seven eyes in 18 patients were diagnosed with CMVR by the indirect ophthalmoscopy. UWF imaging missed the diagnosis in 1 eye because of a zone 3 CMVR lesion. The UWF image showed several CMVR patterns and locations: hemorrhagic necrotizing lesion, granular lesion, frosted branch angiitis, and optic neuropathy lesion. The concordance of the 2 approaches was excellent for the diagnosis of CMVR, classification of CMVR pattern, and location of CMVR. The detection rates of UWF imaging and indirect ophthalmoscopy were 14.0% (26/186; 95% CI 0.089-0.190) and 14.5% (27/186; 95% CI 0.094-0.196), respectively (p = 1.000). The sensitivity and specificity of UWF imaging were 96.3 and 100%, respectively. CONCLUSIONS: UWF imaging is capable of documentation of different CMVR lesions and AIDS-related CMVR screening when examination by an ophthalmologist is not available.

Sensitivity of magnetic resonance tomographic angiography for detecting the degree of neurovascular compression in trigeminal neuralgia.

PURPOSE: Neurovascular compression (NVC) is hypothesized to be the main pathogenic factor of trigeminal neuralgia (TN). Microvascular decompression (MVD) has become a popular surgery for TN, and the success rate depends on the degree of NVC. As the routine examination before MVD, magnetic resonance tomographic angiography (MRTA) shows high sensitivity for detecting NVC. However, there are no reports on the sensitivity of MRTA for assessing the degree of NVC. METHODS: This study aimed to evaluate the sensitivity of MRTA for determining the degree of NVC by comparing preoperative MRTA and intraoperative endoscopy findings. A total of 480 patients who suffered from TN and underwent MVD were included. Their preoperative MRTA and intraoperative endoscopy findings were reviewed. The kappa test was used to identify similarities between the MRTA and endoscopy findings. RESULTS: The degree of NVC on preoperative MRTA was similar to that on endoscopy (kappa = 0.770). The number of offending vessels according to preoperative MRTA was coincident with that according to endoscopy (kappa = 0.722). CONCLUSION: MRTA had high sensitivity for detecting not only the presence of NVC but also the degree of NVC.