MORPHOLOGICAL BIOMARKERS PREDICTING EXUDATIVE CONVERSION IN TYPE 1 NONEXUDATIVE MACULAR NEOVASCULARIZATION USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To investigate the incidence and morphological biomarkers to predict the exudative conversion in eyes with type 1 nonexudative macular neovascularization using swept-source optical coherence tomography angiography. METHODS: Macular neovascularizations were detected using the retinal pigment epithelium-to-retinal pigment epithelium-fit slab of swept-source optical coherence tomography angiography scan. Depending on whether exudation developed within a year, the eyes were divided into two groups: active and silent. Qualitative and quantitative optical coherence tomography angiography parameters of the two groups were evaluated to discriminate the biomarkers associated with exudative conversion. RESULTS: Of the 40 eyes, nine developed exudation within 1 year (incidence rate 22.5%). The active group exhibited a significantly higher "anastomosis and loops" pattern, greater "vessel density," increased "junction density," fewer "number of end points," and lower "lacunarity" compared with the silent group. "Anastomosis and loops" and higher "vessel density" were correlated with the active group in multivariate analyses. A predictive model combining these biomarkers achieved 95% accuracy in predicting exudative conversion. CONCLUSION: At 12 months, the risk of exudation was 22.5%, and "anastomosis and loops" and "vessel density" were useful optical coherence tomography angiography biomarkers for predicting exudative conversion in eyes with type 1 nonexudative macular neovascularization. For eyes with a high risk of exudative conversion, more frequent follow-up is recommended.

Clinical features of primary and compound forms of wide macular posterior staphyloma in high myopia.

BACKGROUND: To compare the ocular features of highly myopic eyes with posterior staphyloma of wide macular type according to its morphological complexity. METHODS: In this cross-sectional study, wide macular posterior staphyloma (WMPS) was classified into the primary (Curtin type I) and the compound (Curtin types VI to X) forms based on the configuration within the staphyloma. The grades of myopic maculopathy and the thicknesses of choroid and sclera were compared between the primary and compound forms of WMPS. RESULTS: A total of 154 eyes (103 patients) with primary WMPS and 65 eyes (49 patients) with compound WMPS were included. Eyes with compound WMPS had worse visual acuity (P = 0.001) and greater axial length (P < 0.001) than those with primary WMPS. Compared to primary WMPS, compound WMPS had a higher grade of myopic macular degeneration (P < 0.001) and a higher frequency of lamellar or full-thickness macular hole associated with myopic traction (21.5% vs. 10.4%; P = 0.028) and active or scarred myopic choroidal neovascularization (33.8% vs. 20.1%; P = 0.030). On swept-source optical coherence tomography, eyes with compound WMPS had significantly thinner choroid and sclera. CONCLUSIONS: The compound form of WMPS had more severe myopic macular changes and worse visual prognosis compared to the primary form of WMPS, and these were associated with more structural deformation in the posterior eyeball. Compound WMPS should be considered as an advanced form of staphyloma.

Early Developmental Characteristics and Features of a Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis.

X-linked juvenile retinoschisis (XLRS) is a hereditary retinal degeneration affecting young males caused by mutations in the retinoschisin (RS1) gene. We generated human induced pluripotent stem cells (hiPSCs) from XLRS patients and established three-dimensional retinal organoids (ROs) for disease investigation. This disease model recapitulates the characteristics of XLRS, exhibiting defects in RS1 protein production and photoreceptor cell development. XLRS ROs also revealed dysregulation of Na/K-ATPase due to RS1 deficiency and increased ERK signaling pathway activity. Transcriptomic analyses of XLRS ROs showed decreased expression of retinal cells, particularly photoreceptor cells. Furthermore, relevant recovery of the XLRS phenotype was observed when co-cultured with control ROs derived from healthy subject during the early stages of differentiation. In conclusion, our in vitro XLRS RO model presents a valuable tool for elucidating the pathophysiological mechanisms underlying XLRS, offering insights into disease progression. Additionally, this model serves as a robust platform for the development and optimization of targeted therapeutic strategies, potentially improving treatment outcomes for patients with XLRS.

DETECTION AND LOCALIZATION OF RETINAL BREAKS IN ULTRAWIDEFIELD FUNDUS PHOTOGRAPHY USING a YOLO v3 ARCHITECTURE-BASED DEEP LEARNING MODEL.

PURPOSE: We aimed to develop a deep learning model for detecting and localizing retinal breaks in ultrawidefield fundus (UWF) images. METHODS: We retrospectively enrolled treatment-naive patients diagnosed with retinal break or rhegmatogenous retinal detachment and who had UWF images. The YOLO v3 architecture backbone was used to develop the model, using transfer learning. The performance of the model was evaluated using per-image classification and per-object detection. RESULTS: Overall, 4,505 UWF images from 940 patients were used in the current study. Among them, 306 UWF images from 84 patients were included in the test set. In per-object detection, the average precision for the object detection model considering every retinal break was 0.840. With the best threshold, the overall precision, recall, and F1 score were 0.6800, 0.9189, and 0.7816, respectively. In the per-image classification, the model showed an area under the receiver operating characteristic curve of 0.957 within the test set. The overall accuracy, sensitivity, and specificity in the test data set were 0.9085, 0.8966, and 0.9158, respectively. CONCLUSION: The UWF image-based deep learning model evaluated in the current study performed well in diagnosing and locating retinal breaks.

RETINITIS PIGMENTOSA SINE PIGMENTO: Clinical Spectrum and Pigment Development.

PURPOSE: To investigate the clinical findings, natural course, and pigment development of patients with retinitis pigmentosa (RP) sine pigmento using multimodal imaging. METHODS: We reviewed the medical records of 810 consecutive patients with RP and assessed serial ultra-widefield fundus photography, fundus autofluorescence, and optical coherence tomography images. Electrophysiological and visual field analysis findings were also reviewed. RESULTS: Of the 774 patients with RP who met the inclusion criteria, 88 were diagnosed with RP sine pigmento, with a prevalence of 11.4%. The mean age of the patients was 35.57 years compared with 49.83 years for patients with typical RP. Fifty-nine patients (67%) demonstrated minimal color change, whereas 29 (33%) presented with grayish flecks in the retinal pigment epithelium on fundus photography. All patients with RP sine pigmento had abnormalities on fundus autofluorescence, and the commonest fundus autofluorescence findings were punctate or reticular hypoautofluorescence. Of the 62 patients without pigmentation at the first visit and at the follow-up visits, 14 (22.6%) had developed pigmentation at their follow-up visit, with an average time of 3.92 years. Most patients retained a visual acuity of ≥20/50 within the age of 50 years. CONCLUSION: Diagnosing RP sine pigmento based solely on ophthalmoscopic findings is more difficult than in more typical cases. Multimodal imaging can provide insights into the clinical characteristics to facilitate the diagnosis, classification, and follow-up of patients.

Swept-source optical coherence tomography angiography of retinal occlusive vasculitis following brolucizumab administration: a case report.

BACKGROUND: We present a case of retinal occlusive vasculitis following brolucizumab administration and the first report of optical coherence tomography angiography (OCTA) findings after treatment. CASE PRESENTATION: A 71-year-old man complained of vision loss in the left eye 6 weeks after brolucizumab injection. His visual acuity was counting fingers, and examination revealed 1 + anterior chamber cells with 2 + vitreous cells. Fundus examination demonstrated vitreous haze, retinal whitening, and vascular sheathing. Fluorescein angiography revealed filling defects in the retinal arteries and veins, and OCTA showed extensive capillary nonperfusion. Under the diagnosis of brolucizumab-associated intraocular inflammation (IOI) and retinal occlusive vasculitis, topical, sub-Tenon, and systemic corticosteroids were administered. After the treatment, visual acuity improved to 20/200, and OCTA revealed gradual improvement in capillary dropout; however, with the limited improvement of reperfusion in the perifoveal areas. CONCLUSIONS: Prompt evaluation and intensive corticosteroid treatments are required for brolucizumab-associated IOI. OCTA imaging provides detailed information on microvascular changes in the retinal vascular plexuses in brolucizumab-associated retinal occlusive vasculitis.

MICROSTRUCTURAL CHANGES IN CYSTOID MACULAR EDEMA IN RETINITIS PIGMENTOSA AFTER INTRAVITREAL DEXAMETHASONE IMPLANT INJECTION.

PURPOSE: To evaluate microstructural changes in cystoid macular edema in retinitis pigmentosa after intravitreal dexamethasone implant injection. METHODS: In an extended cohort of a randomized trial of intravitreal dexamethasone implant for the management of retinitis pigmentosa-associated cystoid macular edema, microstructural changes during six months after the treatment were evaluated using spectral-domain optical coherence tomography. RESULTS: Forty-two eyes were included, and all had cystoid space in the inner nuclear layer (INL) at baseline. No eyes showed subretinal fluid, and 28.6% showed hyperreflective foci. Among 38 eyes with cystoid space both in the INL and outer nuclear layer/Henle's layer, 13 (34.2%) showed complete resolution and 12 (31.6%) showed cystoid space only in the INL at 2 months after injection, whereas others showed persistent cystoid space in both layers. After complete resolution, cystoid space recurrence was earlier in the INL than in the outer nuclear layer/Henle's layer. Multivariable analysis showed that greater cystoid space area in the INL and outer nuclear layer/Henle's layer, presence of macular leakage, and longer intact external limiting membrane at baseline were associated with greater cystoid space area decrease after the treatment. CONCLUSION: Resolution and recurrence pattern of retinitis pigmentosa-associated cystoid macular edema after dexamethasone treatment showed that the INL is the primary layer of cystic change, and this suggests its pathogenesis is most likely caused by Müller cell dysfunction.

Title: efficacy of intravitreal dexamethasone implant on hard exudate in diabetic macular edema.

BACKGROUND: To investigate the effect of intravitreal dexamethasone implant (DEX implant) on hard exudate (HE) accompanying diabetic macular edema (DME). METHODS: This study was a non-comparative non-randomized 1-year prospective interventional study. Patients with DME and HE were treated using DEX implant two or three times. Color fundus photography and optical coherence tomography (OCT) were performed at every visit. HE area was measured semi-automatically from the fundus photographs. RESULTS: Thirty-five patients completed the study. Eleven patients (31.4%) received two injections, while the remaining received three times. HE area (primary outcome) significantly decreased from 1.404±2.094 mm2 (baseline) to 0.212±0.592 mm2 (last visit), which was 24% of the baseline HE area (P<0.001). HE1500 (HE within 1500 µm from the fovea) area also decreased significantly from 0.382±0.467 mm2 to 0.066±0.126 mm2 (P<0.001). Furthermore, anaverage best corrected visual acuity (BCVA) improvement of 4.4 Early Treatment Diabetic Retinopathy Study (ETDRS) letters was observed (from 49.9±18.3 to 54.3±20.4 letters) (P= 0.008). Central macular thickness (CMT) decreased from 455.8±23.6 µm to 366.8±31.1 µm (P=0.009). Repetitive measurements for entire study duration was analyzed using generalized estimating equations (GEE), where BCVA was related to age, CMT, and HE1500 area in multivariate analyses. CONCLUSION: DEX implant could reduce and suppress HE in DME for one year with two or three injections. And centrally located HE area (HE1500 area) is related to vision. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02399657 , Registered 26 March 2015.

The diagnostic application of targeted re-sequencing in Korean patients with retinitis pigmentosa.

BACKGROUND: Identification of the causative genes of retinitis pigmentosa (RP) is important for the clinical care of patients with RP. However, a comprehensive genetic study has not been performed in Korean RP patients. Moreover, the genetic heterogeneity found in sensorineural genetic disorders makes identification of pathogenic mutations challenging. Therefore, high throughput genetic testing using massively parallel sequencing is needed. RESULTS: Sixty-two Korean patients with nonsyndromic RP (46 patients from 18 families and 16 simplex cases) who consented to molecular genetic testing were recruited in this study and targeted exome sequencing was applied on 53 RP-related genes. Causal variants were characterised by selecting exonic and splicing variants, selecting variants with low allele frequency (below 1 %), and discarding the remaining variants with quality below 20. The variants were additionally confirmed by an inheritance pattern and cosegregation test of the families, and the rest of the variants were prioritised using in-silico prediction tools. Finally, causal variants were detected from 10 of 18 familial cases (55.5 %) and 7 of 16 simplex cases (43.7 %) in total. Novel variants were detected in 13 of 20 (65 %) candidate variants. Compound heterozygous variants were found in four of 7 simplex cases. CONCLUSION: Panel-based targeted re-sequencing can be used as an effective molecular diagnostic tool for RP.

Selective retina therapy with real-time feedback-controlled technology in central serous chorioretinopathy: a 24-month follow-up real-world prospective study.

OBJECTIVE: Although central serous chorioretinopathy (CSC) treatment using selective retinal therapy (SRT) has presented favourable outcomes, no long-term studies with a real-world clinical practice regimen have been conducted. METHODS AND ANALYSIS: We performed a long-term assessment of CSC treatment using SRT with real-time feedback (RTF) technology. 50 patients (53 eyes) with CSC and more than a 1-month symptom duration were recruited and treated with SRT using a 1.7 µs pulse width, 527 nm neodymium-doped yttrium lithium fluoride (Nd:YLF) laser equipped with an RTF system. RESULTS: After 6 months of treatment, complete subretinal fluid resolution was achieved in 62% of the eyes. The mean best-corrected visual acuity (BCVA; logarithm of the minimum angle of resolution, mean±SD) improved slightly from 0.15±0.18 at baseline to 0.12±0.21 at 6 months (p=0.062). The central retinal thickness (CRT; mean±SD) was reduced significantly from 350.6±100.1 µm at baseline to 268.2±70.6 µm at 6 months (p<0.001). Long-term follow-up revealed significant improvements in BCVA, from 9 months until 24 months, and in CRT, from 1 month until 24 months. No treatment-related adverse events were observed during the 24-month follow-up period. CONCLUSION: Our results suggest that SRT with RTF technology is a long-term safe treatment with anatomical improvement for patients with CSC.

Longer axial length is associated with better prediction for refractive error after sutureless flanged intrascleral fixation of intraocular lens.

OBJECTIVE: To investigate refractive outcomes and associated factors after sutureless flanged intrascleral fixation of intraocular lens (SFIF-IOL). METHODS: We retrospectively reviewed the medical records of consecutive patients who underwent SFIF-IOL at a single centre. The prediction error (PE; difference between the achieved and target refractive error) and absolute PE (APE) were analysed. Risk factors associated with refractive surprise, defined as APE > +0.5 D, were investigated using multivariable logistic regression analysis. RESULTS: Ninety-one eyes were included. At the final follow-up, the mean PE and APE were +0.07 ± 0.88 and +0.68 ± 0.56 D, respectively. Refractive surprise was observed in 44 eyes (54.3%) and was associated with a shorter axial length (AL) [odds ratio, 0.825; 95% confidence interval, 0.688-0.991; P = 0.039]. APE showed a significant correlation with AL at the final visit (⍴ = -0.269, P = 0.010), and eyes with AL ≥ 26 mm had significantly lower APE than did those with AL of 24-26 mm (P = 0.021) and AL < 24 mm (P = 0.0059). CONCLUSIONS: The refractive outcome after SFIF-IOL using manufacturer's A constant was favourable on average. Eyes with a longer AL were more likely to show a smaller deviation from the target refraction.

The effect of glycosylated hemoglobin levels on the response to intravitreal dexamethasone implant for treating diabetic macular edema.

This study investigates the impact of glycosylated hemoglobin (HbA1c) on the efficacy of intravitreal dexamethasone (DEX) implants in patients with diabetic macular edema (DME) over a 12-month period. We retrospectively reviewed 90 DME patients treated with DEX implants, categorizing them based on baseline HbA1c levels (≤ 7% and > 7%) and 12-month changes in HbA1c ("improved", "stable", "worsened"). At the 2-month mark, the mean central subfield thickness (CST) reduction in the HbA1c ≤ 7% group was - 147.22 ± 113.79 µm compared to -130.41 ± 124.50 µm in the > 7% group (p = 0.506). Notably, 12-month outcomes between these groups showed no significant difference. The "improved" HbA1c subgroup experienced a more pronounced CST reduction at 2 months (p = 0.042), with outcomes leveling off with other groups by 12 months. Conclusively, DEX implant outcomes in DME were not influenced by either baseline HbA1c levels or their changes over time. This suggests that local alterations in the inflammation milieu may have a potentially stronger impact on DME treatment outcomes, highlighting the importance of considering local factors in DME treatment.

Quantitative microvascular analysis in different stages of retinitis pigmentosa using optical coherence tomography angiography.

As retinitis pigmentosa (RP) is chronic and progressive, the chronological sequence of microvascular changes is important for understanding its pathophysiology. We aimed to investigate retinal and choroidal microvascular changes according to the RP stages. The stages of RP were classified into three stages according to the integrity and width of the inner segment ellipsoid zone: early, ≥ 2500 µm; moderate, < 2500 µm; advanced, absence. Using optical coherence tomography angiography, quantitative microvascular parameters were analyzed. In total, 91 eyes from 49 patients were included. For the superficial capillary plexus (SCP) and deep capillary plexus (DCP), perfusion densities (PDs) in the early stage (SCP: 37.32 ± 8.11%; DCP: 21.19 ± 9.15%) were greater than those in moderate (SCP: 34.16 ± 6.65%, P = 0.011; DCP: 15.67 ± 8.85%, P = 0.031) and advanced stages (SCP: 33.71 ± 9.02%, P = 0.030; DCP: 12.83 ± 6.29%, P < 0.001). The choroidal vascularity index in the early stage (0.58 ± 0.03) was greater than those in the moderate (0.57 ± 0.02, P = 0.017) and advanced stage (0.56 ± 0.02, P = 0.033). The area and perimeter of foveal avascular zone (FAZ) in advanced stage (0.44 ± 0.26 mm2, 2.96 ± 0.86 mm, respectively) were larger than those in early (0.26 ± 0.11 mm2, P = 0.020; 2.19 ± 0.53 mm, P = 0.006, respectively) and moderate stage (0.28 ± 0.13 mm2, P = 0.043; 2.24 ± 0.67 mm, P = 0.013, respectively). During RP disease progression, retinal and choroidal microvascular vessel density decreases in the early stage, followed by FAZ enlargement in the advanced stage.

Prediction of Axial Length From Macular Optical Coherence Tomography Using Deep Learning Model.

Purpose: The purpose of this study was to develop a deep learning model for predicting the axial length (AL) of eyes using optical coherence tomography (OCT) images. Methods: We retrospectively included patients with AL measurements and OCT images taken within 3 months. We utilized a 5-fold cross-validation with the ResNet-152 architecture, incorporating horizontal OCT images, vertical OCT images, and dual-input images. The mean absolute error (MAE), R-squared (R2), and the percentages of eyes within error ranges of ±1.0, ±2.0, and ±3.0 mm were calculated. Results: A total of 9064 eyes of 5349 patients (total image number of 18,128) were included. The average AL of the eyes was 24.35 ± 2.03 (range = 20.53-37.07). Utilizing horizontal and vertical OCT images as dual inputs, deep learning models predicted AL with MAE and R2 of 0.592 mm and 0.847 mm, respectively, in the internal test set (1824 eyes of 1070 patients). In the external test set (171 eyes of 123 patients), the deep learning models predicted AL with MAE and R2 of 0.556 mm and 0.663 mm, respectively. Regarding error margins of ±1.0, ±2.0, and ±3.0 mm, the dual-input models showed accuracies of 83.50%, 98.14%, and 99.45%, respectively, in the internal test set, and 85.38%, 99.42%, and 100.00%, respectively, in the external test set. Conclusions: A deep learning-based model accurately predicts AL from OCT images. The dual-input model showed the best performance, demonstrating the potential of macular OCT images in AL prediction. Translational Relevance: The study provides new insights into the relationship between retinal and choroidal structures and AL elongation using artificial intelligence models.

Long-Term Efficacy of Inferior Oblique Myectomy Accompanied with Tenon's Capsule Closure: Objective Analysis Using Nine-Gaze Photographs.

Background: The aim is to evaluate the long-term efficacy of inferior oblique (IO) myectomy combined with Tenon's capsule closure to prevent muscle reattachment to the sclera. Methods: We retrospectively reviewed the medical records of 18 patients with primary and secondary IO overaction who underwent IO myectomy accompanied by Tenon's capsule closure. Patients were followed up for at least 1 year after the surgery. The main outcome measures included oblique muscle dysfunction, which was objectively graded through computerized analysis of nine-gaze photographs, and the amount of vertical deviation in the primary position using alternate prism cover testing. Results: After a mean follow up of 2.5 years, the grade of IO overaction decreased from +2.2 ± 1.0 to -0.8 ± 1.0 (p < 0.001). In patients with secondary IO overaction with superior oblique (SO) palsy, SO underaction improved from -2.2 ± 1.5 to -0.2 ± 1.8 (p = 0.006). Successful vertical deviation in the primary position of seven prism diopters or less was achieved in 83.3% of the patients. Underaction of the IO was observed in 11.1% of patients, whereas none of the patients showed antielevation syndrome. Conclusion: IO myectomy combined with Tenon's capsule closure might be safe and effective for the treatment of primary and secondary IO overaction in the long term.

Deep Learning-based Prediction of Axial Length Using Ultra-widefield Fundus Photography.

PURPOSE: To develop a deep learning model that can predict the axial lengths of eyes using ultra-widefield (UWF) fundus photography. METHODS: We retrospectively enrolled patients who visited the ophthalmology clinic at the Seoul National University Hospital between September 2018 and December 2021. Patients with axial length measurements and UWF images taken within 3 months of axial length measurement were included in the study. The dataset was divided into a development set and a test set at an 8:2 ratio while maintaining an equal distribution of axial lengths (stratified splitting with binning). We used transfer learning-based on EfficientNet B3 to develop the model. We evaluated the model's performance using mean absolute error (MAE), R-squared (R2), and 95% confidence intervals (CIs). We used vanilla gradient saliency maps to illustrate the regions predominantly used by convolutional neural network. RESULTS: In total, 8,657 UWF retinal fundus images from 3,829 patients (mean age, 63.98 ±15.25 years) were included in the study. The deep learning model predicted the axial lengths of the test dataset with MAE and R2 values of 0.744 mm (95% CI, 0.709-0.779 mm) and 0.815 (95% CI, 0.785-0.840), respectively. The model's accuracy was 73.7%, 95.9%, and 99.2% in prediction, with error margins of ±1.0, ±2.0, and ±3.0 mm, respectively. CONCLUSIONS: We developed a deep learning-based model for predicting the axial length from UWF images with good performance.

Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics. Methods: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0. Results: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment. Conclusions: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.

Effect of fiber entanglement in chopped glass fiber reinforced composite manufactured via long fiber spray-up molding.

Long Fiber Spray-up Molding (LFSM) deviates from the conventional approach in liquid composite molding (LCM) processes by utilizing extremely long chopped strands of fibers as the primary reinforcement material in its fabrication process. In LFSM, chopped fibers are impregnated with resin that is sprayed vertically downwards before reaching the mold surface. The spraying mechanism is mounted on an actuator, which is capable of spraying freely in any specified pattern or direction. Under LFSM, it is extremely difficult to fabricate a composite part with uniformly distributed fiber content throughout its volume. The consequences of the non-uniform fiber volume distribution arise from the fiber entanglement as the length of the fiber reaches up to 100 mm in LFSM. In this study, the effect of fiber entanglement during LFSM was analyzed through various approaches. This included measuring the coefficient of friction between fibers in contact and examining the correlation between fiber lengths and the number of intersections. Furthermore, the viscoelastic properties of the uncured composite part were assessed by experimenting with the influence of viscosity on fiber length during compression molding. The results were then computed, modeled, and visualized in MATLAB, considering variations in viscosity and fiber length, both before and after compression molding.

Clinical and genetic features of Koreans with retinitis pigmentosa associated with mutations in rhodopsin.

Purpose: To investigate the clinical features, natural course, and genetic characteristics of Koreans with rhodopsin-associated retinitis pigmentosa (RHO-associated RP). Design: We conducted a retrospective, multicenter, observational cohort study. Participants: We reviewed the medical records of 42 patients with RHO-associated RP of 36 families who visited 4 hospitals in Korea. Methods: Patients with molecular confirmation of pathogenic variants of the RHO gene were included. The patients were divided into two subgroups: the generalized and sector RP groups. A central visual field of the better-seeing eye of <10° or a best-corrected visual acuity of the better-seeing eye <20/40 indicated the progression to late-stage RP. Results: The mean age at which symptoms first appeared was 26.3 ± 17.9 years (range: 8-78 years), and the mean follow-up period was 80.9 ± 68.7 months (range: 6-268 months). At the last follow-up visit, the generalized RP group showed a significantly higher rate of visual field impairment progression to late-stage RP than that of the sector RP group (22 of 35 [62.9%] vs. 0 of 7 [0.0%], p = 0.003). No cases in the sector RP group progressed to generalized RP. Best-corrected visual acuity deterioration to late-stage RP was observed only in the generalized RP group (13 of 35 patients; 37.1%), whereas no deterioration was observed in the sector RP group. We identified 16 known and three novel RHO mutations, including two missense mutations (p.T108P and p.G121R) and one deletion mutation (p.P347_A348del). The pathogenic variants were most frequently detected in exon 1 (14 of 36 [38.9%]). The most common pathogenic variants were p.P347L and T17M (5 of 36 [13.9%] families). Among 42 patients of 36 families, 35 patients of 29 families (80.6%) presented with the generalized RP phenotype, and seven patients of seven families (19.4%) presented with the sector RP phenotype. Three variants (p.T17M, p.G101E, and p.E181K) presented with both the generalized and sector RP phenotypes. Conclusion: This multicenter cohort study provided information on the clinical and genetic features of RHO-associated RP in Koreans. It is clinically important to expand the genetic spectrum and understand genotype-phenotype correlations to ultimately facilitate the development of gene therapy.

Longitudinal Microstructure Changes of the Retina and Choroid in Retinitis Pigmentosa.

PURPOSE: To investigate longitudinal changes in the retinal and choroidal microstructure of the macula in patients with retinitis pigmentosa (RP). DESIGN: Retrospective, observational cohort study. METHODS: A total of 69 patients with RP and 69 age- and sex-matched controls who underwent optical coherence tomography (OCT) over a 4-year follow-up period were included. The severity of RP was classified into 3 stages according to the integrity of the inner segment ellipsoid zone. The retinal and choroidal layers were segmented manually from OCT images. The areas of retinal pigment epithelium (RPE) atrophy and choroidal vascular index (CVI) were also analyzed. Longitudinal changes in the OCT parameters were compared among the groups. RESULTS: Significant decreases (median [interquartile range]) in the thickness of the ganglion cell inner plexiform layer (GCIPL; -1.04 [-2.41 to -0.17]), outer nuclear layer (ONL; -1.44 [-1.86 to -0.28]), and inner segment ellipsoid (ISE; -0.74 [-1.33 to -0.49]) at the moderate stage and retinal nerve fiber layer (RNFL; -1.49 [-2.08 to -0.66]) and GCIPL (0.58 [-1.79 to 0.06]) at the advanced stage were observed. Choroidal thickness decreased significantly from -7.62 to -9.40 µm per year at all stages. RPE atrophy and CVI reduction were observed at the advanced stage. There was no change in the control group. CONCLUSIONS: ONL and GCIPL thicknesses decreased at the moderate and advanced stages of RP; RNFL thickness decreased only at the advanced stage; and choroidal thickness decreased continuously. In addition, RPE atrophy and CVI reduction were prominent at the advanced stage. These results indicate that there is a temporal variation in the damage of each retinal layer and the choroid in RP patients.