Case series of branch retinal vein occlusion secondary to rhegmatogenous retinal detachment and its surgical management.

BACKGROUND: To review cases of branch retinal vein occlusion (BRVO) secondary to rhegmatogenous retinal detachment (RRD) and its surgical management and presume their mechanism. METHODS: Medical records of patients who underwent surgery for RRD between 2015 and 2019 at a single tertiary care center were retrospectively reviewed. New BRVO secondary to RRD or its surgical procedure was diagnosed based on the fundus examination and its clinical course. RESULTS: A total of 734 RRD surgeries were performed for five years, and six cases of new BRVOs were noticed in the first year after surgery (incidence was 0.68%: six cases of BRVO / 734 cases of surgical RRD); five cases occurred after vitrectomy, and one occurred after scleral buckling. In three cases, retinal veins were presumed to already be partially occluded related due to a kink of the retinal vein seen before surgery. In the other three cases, the retinal veins were presumed to have incurred damage during vitrectomy. CONCLUSION: In the present cohort, RRD or its related procedures caused BRVO within a year of surgery at an incidence of 0.68%. The proposed mechanisms are kinks of the retinal vein on the detached retina and damage to the retinal vein during vitrectomy.

Quantitative evaluation of hard exudates in diabetic macular edema after short-term intravitreal triamcinolone, dexamethasone implant or bevacizumab injections.

BACKGROUND: To quantitatively compare short-term hard exudates (HEs) alteration in patients with diabetic macular edema (DME) after intravitreal triamcinolone, dexamethasone implant or bevacizumab injections. METHODS: This retrospective study enrolled DME eyes with HEs that underwent a single-dose intravitreal injection of triamcinolone (25 eyes), dexamethasone implant (20 eyes), or three monthly injections of bevacizumab (25 eyes) and completed at least three months of follow-up. All patients were examined before and after 1, 2 and 3 months of injections. Using color fundus photographs, the amount of HEs was quantified by two masked graders. The difference in HEs area between baseline and each follow-up visit was compared among the three groups. RESULTS: After three months, HEs area was reduced to 52.9 ± 4.21% (P < 0.001) in the triamcinolone group, 63.6 ± 6.08% (P = 0.002) in the dexamethasone implant group, and 85.2 ± 5.07% (P = 0.198) in the bevacizumab group. A significant reduction in HEs appeared at one month in the triamcinolone group (53.5 ± 4.91%, P < 0.001) and at two months in the dexamethasone implant group (70.1 ± 5.21%, P = 0.039). CONCLUSIONS: Our study suggests intravitreal steroids (triamcinolone, dexamethasone implants) significantly reduce HEs in DME patients on short-term follow-up, whereas intravitreal bevacizumab does not. Therefore, intravitreal steroids may be useful in DME with HEs in the fovea.

Hemodialysis-induced positional changes in lamina cribrosa.

This study is aimed to investigate the effect of hemodialysis (HD) on the lamina cribrosa (LC) of the optic nerve head (ONH) using swept-source optical coherence tomography (SS-OCT) and other ophthalmological parameters in patients with end-stage kidney disease (ESKD). This prospective observational study included 29 patients who underwent HD for ESKD. ONH parameters including neural canal diameter (NCD), peripapillary vertical height (PVH), and anterior LC depth (LCD), were assessed using SS-OCT. Changes in the ONH parameters before and after HD were statistically analysed. Correlations between changes in the LCD and other ocular and systemic measurements were identified using Pearson's correlation analyses. The mean anterior LCD significantly decreased from 441.6 ± 139.8 µm before HD to 413.5 ± 141.7 µm after HD (P = 0.001). Mean NCD and PVH did not show significant changes after HD (P = 0.841 and P = 0.574, respectively). A significant correlation was found between changes in the anterior LCD and the mean ocular perfusion pressure (r = 0.397, P = 0.036). We observed a significant decrease in anterior LCD after HD. Our study suggests that HD can influence the ONH, especially in the LC.

Expression of microRNAs related to apoptosis in the aqueous humor and lens capsule of patients with glaucoma.

Background: The aim of this study is to investigate the expression profiles of microRNAs (miRNAs) related to apoptosis in the aqueous humor (AH) and lens capsule (LC) of patients with glaucoma. Methods: AH and LC samples were collected from patients with open-angle glaucoma and control participants who were scheduled for cataract surgery. A miRNA PCR array comprising 84 miRNAs was used to analyze the AH (glaucoma, n = 3; control, n = 3) and LC samples (glaucoma, n = 3; control, n = 4). Additionally, the AH and LC samples (glaucoma, n = 3; control, n = 4) were subjected to quantitative real-time PCR to validate the differentially expressed miRNAs determined using the PCR array. Bioinformatics analysis was performed to identify the interactions between miRNAs and diseases. Additionally, the differential expression of these miRNAs and the target gene was validated through in vitro experiments using a retinal ganglion cell (RGC) model. Results: Expression levels of 19 and 3 miRNAs were significantly upregulated in the AH and LC samples of the glaucoma group, respectively (p < 0.05). Of these, the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p showed significant differences in both AH and LC samples. Bioinformatics analysis showed experimentally validated 8 miRNA:gene pairs. Among them, PTEN was selected to analyze the expression level in AH and LC from separate cohort (glaucoma, n = 5; control, n = 4). The result showed downregulation of PTEN concurrent with upregulation of the two miRNAs in LC samples of glaucoma group. In vitro experiments validated that the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p were significantly upregulated, and that of PTEN was significantly downregulated in the H2O2-treated RGC, while the level of PTEN was recovered through co-treatment with miR-193a inhibitor or miR-222 inhibitor. Conclusion: This is the first study to investigate the differential expression of apoptosis-related miRNAs in the AH and LC of patients with glaucoma. Hsa-miR-193a-5p and hsa-miR-222-3p, which were upregulated in both AH and LC, may be considered potential biomarkers for glaucoma.

Risk factors for development of anti-adalimumab antibodies in non-infectious uveitis.

Purpose: To evaluate risk factors associated with development of anti-adalimumab antibodies (AAA) in patients with non-infectious uveitis treated with adalimumab. Methods: A retrospective, cross-sectional, case-control study was done evaluating patients with non-infectious uveitis treated with adalimumab for at least 12 months and have undergone testing for AAA levels. Demographics, clinical characteristics, grading of ocular inflammation, and previous and concomitant immunomodulatory therapy were assessed. Univariate and multivariate analysis were done to estimate odds ratio (OR) with 95% confidence intervals for the various risk factors. Results: A total of 31 patients were included in the analysis, in which 12 patients who tested positive (Group 1) were matched with 19 patients who tested negative for AAA (Group 2). The groups differed significantly in terms of sex (female) (91.7% vs 52.6%, p = 0.046), presence of systemic disease (91.7% vs 42.1%, p = 0.008), and presence of anterior chamber inflammation at baseline (100% vs 63.2%, p = 0.026). A history of interruption in anti-TNF therapy prior to starting or restarting adalimumab was found to have an increased odds for development of AAA (OR 16.89 [2.92, 107.11], p = 0.008), as well as flare-ups (reactivation of disease) during adalimumab therapy (OR 6.77 [1.80, 61.80], p = 0.027). Weekly dosing of adalimumab was shown to decrease odds of AAA development (OR 0.34 [0.02, 0.70], p = 0.040), while concomitant anti-metabolite therapy was not shown to be a statistically significant protective factor (OR 2.22 [0.50, 9.96], p = 0.148). Conclusions: History of interruption in anti-TNF therapy and flare during adalimumab were associated with development of AAA, while weekly dosing of adalimumab was protective against AAA. Identification of those with higher risk of developing AAA may guide in clinical decision making to optimize management for these patients.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.

Outer photoreceptor layer thickness mapping in normal eyes and eyes with various macular diseases using spectral domain optical coherence tomography: a pilot study.

BACKGROUND: To obtain a de novo map of outer photoreceptor layer (OPRL) thickness using a semiautomatic segmentation method for commercial spectral-domain optical coherence tomography (SD-OCT) and analyze the features of the resulting OPRL map in normal eyes and eyes with various inactive macular diseases. METHODS: Forty normal eyes and 50 eyes with various inactive macular diseases such as resolved central serous chorioretinopathy (20 eyes), surgically-repaired macular hole (10 eyes), epiretinal membrane (10 eyes), and reattached rhegmatogenous retinal detachment (10 eyes) were screened. All subjects underwent a 12 radial scan protocol in SD-OCT. The segmentation lines defining the OPRL were modified using built-in software. The diseased eyes were subdivided into two groups (good vision, or intermediate to poor vision) based on a visual acuity better or worse than 20/40. The map of the OPRL thickness was obtained automatically by the embedded software and was presented as the Early Treatment Diabetic Retinopathy Study (ETDRS) style. RESULTS: The mean OPRL thickness in normal eyes in all subfields was 40.37 ± 4.35 µm. The central subfield area showed the greatest mean OPRL thickness in normal eyes. The mean OPRL thickness of diseased eyes with good vision in the central subfield was greater than that of eyes with intermediate to poor vision. The OPRL thickness map showed various patterns according to the type of macular diseases. CONCLUSIONS: We suggest that our semiautomated segmentation method using a 12 radial scan protocol is simple, fast, and suitable for producing a reliable OPRL map with ETDRS. This quantitative data could be useful in clinical practice or research of various macular diseases.

Association of a Bioimpedance Profile with Optical Coherence Tomography Features in Diabetic Macular Edema.

We examined the association between bioimpedance profiles and optical coherence tomography (OCT) features in patients with diabetic macular edema (DME). This cross-sectional study included 100 eyes of 100 patients with type 2 diabetes mellitus. The systemic fluid status was assessed using extracellular water-to-total body water ratio (ECW/TBW) and phase angle (PhA), which was measured using bioimpedance equipment. ECW/TBW was higher in the DR (diabetic retinopathy) with DME group than in the no DR and DR without DME groups (p = 0.007 and p = 0.047, respectively); however, no significant difference was observed between the no DR and DR without DME groups. The PhA values were significantly lower in the DR with DME group (5.45 ± 0.84) than in the no DR (6.69 ± 0.69) and DR without DME groups (6.05 ± 1.15) (p < 0.001, p = 0.032, respectively). The presence of multiple HRF (hyper-reflective foci) was associated with a significantly higher ECW/TBW (p = 0.001). In the group with the most significant HRF, PhA was lower than in those with none or moderate amounts of HRF (p < 0.05). Bioimpedance fluid profiles of patients with OCT features of DME suggest a connection between the overall systemic state, including fluid status and DME development. Further research is required to fully understand and utilize this information for effective clinical assessment and treatment planning.

Neurosarcoidosis, Coccidioidomycosis, or Both!

Purpose: To report a case of neurosarcoidosis (NS) who was initially diagnosed as Coccidioidomycosis immitis (CI) infection. Observations: A 57-year-old diabetic man presented with sudden painless diminution of vision, metamorphopsia, and color vision deficits in the left eye (OS) for one month. His vision was 20/20 in the right eye (OD) and 20/40 OS. Ophthalmic examination revealed left relative afferent pupillary defect, blurred optic nerve margin, creamy chorioretinal infiltration around the optic disc, and mild macular edema. OD examination was non-revealing. Chest CT scan with contrast showed calcified mediastinal lymph nodes, but biopsy of the lymph nodes was normal. Brain and orbit MRI demonstrated soft tissue abnormality with enhancement in left orbital apex with involvement of the extraocular muscles. CSF culture was negative, but complement fixation had positive titer of 1:2 for CI. The patient was diagnosed with CI meningitis, and antifungal therapy was initiated. Slight visual and symptomatic improvement was observed, which was not completely satisfactory. Biopsy of extraocular orbital muscle five months later revealed non-caseating granulomatous inflammation, leading to initiation of prednisone trial therapy. Nine months later, the patient was referred to a tertiary center owing to persistence of optic disc edema OS. PET CT was consistent with a diagnosis of sarcoidosis. Antifungal treatment was discontinued, and oral prednisone with methotrexate was initiated. Subsequently, methotrexate was replaced by infliximab to further manage ocular inflammation and neurologic symptoms which was effective. Vision was 20/20 OD and 20/30 OS at the most recent visit. Conclusion and Importance: Signs and symptoms of neurosarcoidosis and coccidioidomycosis can be similar and deceiving. The index case underscores importance of considering appropriate differential diagnoses in patients with similar symptoms and signs who may respond to preliminary designated treatment but not to the optimal extent. Considering such possibility could assist clinicians in managing the patients timely and efficiently.

Structural and Functional Changes in Non-Paraneoplastic Autoimmune Retinopathy.

BACKGROUND: To describe longitudinal changes in patients with non-paraneoplastic autoimmune retinopathy (npAIR) by utilizing different diagnostic modalities/tests. METHODS: The index study is a retrospective longitudinal review of sixteen eyes of eight patients from a tertiary care eye hospital diagnosed with npAIR. Multiple diagnostic modalities such as wide-angle fundus photography (WAFP), WA fundus autofluorescence (WAFAF), spectral-domain optical coherence tomography (SD-OCT), Goldmann visual field (GVF) perimetry, microperimetry (MP), electrophysiologic testing, and adaptive optics scanning laser ophthalmoscopy (AOSLO) were reviewed and analyzed. RESULTS: At the baseline visits, anomalies were detected by multimodal diagnostic tests on all patients. Subjects were followed up for a median duration of 11.5 [3.0-18.7] months. Structural changes at the baseline were detected in 14 of 16 (87.5%) eyes on WAFP and WAFAF and 13 of 16 (81.2%) eyes on SD-OCT. Eight of the ten (80%) eyes that underwent AOSLO imaging depicted structural changes. Functional changes were detected in 14 of 16 (87.5%) eyes on GVF, 15 of 16 (93.7%) eyes on MP, and 11 of 16 (68.7%) eyes on full-field electroretinogram (ff-ERG). Multifocal electroretinogram (mf-ERG) and visual evoked potential (VEP) tests were performed in 14 eyes, of which 12 (85.7%) and 14 (100%) of the eyes demonstrated functional abnormalities, respectively, at baseline. Compared to all the other structural diagnostic tools, AOSLO had a better ability to demonstrate deterioration in retinal microstructures occurring at follow-ups. Functional deterioration at follow-up was detected on GVF in 8 of 10 (80%) eyes, mf-ERG in 4 of 8 (50%) eyes, and MP in 7 of 16 (43.7%) eyes. The ff-ERG and VEP were stable in the majority of cases at follow-up. CONCLUSIONS: The utilization of multimodal imaging/tests in the diagnosing and monitoring of npAIR patients can aid in identifying anomalous changes over time. Analysis of both the anatomical and functional aspects by these devices can be supportive of detecting the changes early in such patients. AOSLO shows promise as it enables the capture of high-resolution images demonstrating quantifiable changes to retinal microstructure.

Choroidal thickness and volume mapping by a six radial scan protocol on spectral-domain optical coherence tomography.

PURPOSE: To report a 6 radial scan protocol, which simply generates a topographic map of choroidal thickness and volume on a commercial spectral-domain optical coherence tomography (SD-OCT) device. We analyzed the features of the resulting choroidal maps in healthy eyes. DESIGN: Prospective, noncomparative case series. PARTICIPANTS: Eighty eyes from 40 healthy volunteers who visited the healthcare clinic of Hanyang University Hospital from December 2010 to February 2011. METHODS: All participants underwent a 6 radial scanning protocol using an SD-OCT device. In a single session, the device produces 6 high-resolution averaging B-scan images. For segmentation of the choroid layer, the reference lines of the retinal boundary (internal limiting membrane-retinal pigment epithelium) were adjusted to the choroidal boundary (retinal pigment epithelium-choroid/sclera junction) in each of the 6 radial B-scans. A topographic map of choroidal thickness and volume was automatically generated by built-in software according to the Early Treatment Diabetic Retinopathy Study (ETDRS) layout. A statistical analysis was conducted to compare the choroidal thickness and volume measurements for each ETDRS subfield. MAIN OUTCOME MEASURES: An ETDRS-style topographic map of choroidal thickness and volume. RESULTS: The mean time required for segmentation adjustment was 167.4±15.8 seconds. The mean choroidal thickness of all ETDRS subfields was 285.9±53.0 µm, and the mean total choroidal volume of the entire ETDRS area was 7.72±1.2 mm(3). The nasal outer macula area was significantly smaller than any other ETDRS subfield (P<0.05) except for the adjacent superior and inferior outer macula subfields. Refractive error was correlated with choroidal thickness in all ETDRS subfields. Age was also correlated with choroidal thickness for almost all of the ETDRS subfields except for the temporal inner, nasal outer, and temporal outer macula areas. The total choroidal volume was correlated with the refractive error and age. CONCLUSIONS: A 6 radial scan protocol, using a commercial SD-OCT device, enables the production of reliable choroidal thickness and volume maps with an ETDRS layout. By using this protocol, more comprehensive choroidal evaluation is possible in clinical practice or research.

A novel noninvasive detection method for retinal nonperfusion using confocal red-free imaging.

PURPOSE: To report confocal red-free blue reflectance imaging as a novel, noninvasive imaging modality for the detection of retinal nonperfusion and to compare its effectiveness with that of fluorescein angiography (FA) in diabetic retinopathy (DR) and retinal vein occlusion (RVO). DESIGN: Evaluation of diagnostic technology, retrospective observational case series. PARTICIPANTS: We enrolled 54 eyes of 44 patients with DR or RVO that had definite retinal nonperfusion on FA. METHODS: All patients underwent red-free blue reflectance imaging and FA using a confocal scanning laser ophthalmoscope. For all patients, macular and midperipheral retinal nonperfusion were identified on both confocal red-free and corresponding FA images, and were delineated by 2 independent readers. We evaluated the correspondence of the 2 imaging methods by comparing the sizes of the delineated areas and obtaining the overlapping ratio after image processing. MAIN OUTCOME MEASURES: Comparison of size and overlapping correspondence between delineated area of retinal nonperfusion obtained by FA and confocal red-free imaging. RESULTS: Image analysis showed a high correlation (r>0.9) in the mean size of retinal nonperfusion between confocal red-free and corresponding FA images with DR or RVO. Reliable agreement between the 2 methods was confirmed by size comparisons (P = 0.563) and overlapping correspondence (overlapping ratio, 0.76) of the delineated area. CONCLUSIONS: Our findings suggest that confocal red-free imaging is a simple, reliable, safe, and noninvasive method for effectively plotting retinal nonperfusion. This procedure, first reported herein, has the potential to be used for the noninvasive detection and quantification of retinal nonperfusion in screening, initial evaluation, treatment, and follow-up of progressive ischemic retinopathy such as DR and RVO.

Retinopathy of prematurity: a review of epidemiology and current treatment strategies.

Retinopathy of prematurity (ROP) is among the most common causes of childhood blindness. Three phases of ROP epidemics have been observed worldwide since ROP was first described in the 1940s. Despite advances in neonatal care, the occurrence of ROP and associated visual impairment has been increasing somewhere on Earth and remains difficult to control. Conventional treatment options for preventing ROP progression include retinal ablation using cryotherapy or laser therapy. With the emergence of anti-vascular endothelial growth factor (anti-VEGF) treatment for ocular diseases, the efficacy and safety of anti-VEGF therapy for ROP have recently been actively discussed. In the advanced stage of ROP with retinal detachment, surgical treatment including scleral buckling or vitrectomy is needed to maintain or induce retinal attachment. At this stage, the visual outcome is usually poor despite successful anatomical retinal attachment. Therefore, preventing ROP progression by timely screening examinations and treatment remains the most important part of ROP management.

Associations between Choriocapillaris Flow on Optical Coherence Tomography Angiography and Cardiovascular Risk Profiles of Patients with Acute Myocardial Infarction.

We evaluated the association between macular perfusion assessed via optical coherence tomography angiography (OCTA) and the cardiovascular risk profiles of patients with acute myocardial infarction (AMI). Patients with AMI who underwent comprehensive ophthalmological examinations and retinal OCTA were evaluated retrospectively. Retinal OCTA was performed for each patient within 3 days of admission. Quantitative analyses of the vessel density (VD) of the superficial capillary plexus (SCP) layers, deep capillary plexus layers (DCP), and choriocapillaris were performed after image processing. The 10-year risk of atherosclerotic cardiovascular disease (ASCVD), Global Registry of Acute Coronary Events (GRACE) score, reduction of atherothrombosis for continued health (REACH) score, and thrombolysis in myocardial infarction (TIMI) risk score were assessed. Sixty patients were included. VD in SCP and DCP was not associated with a 10-year ASCVD risk; however, choriocapillaris flow void features were significantly correlated with the 10-year ASCVD risk: decreased count, increased average size, and increased signal void area were correlated with increased 10-year ASCVD risk, GRACE score, REACH score, and TIMI risk score. In the multivariate analysis, a 10-year ASCVD risk (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.08) and brain natriuretic peptide (adjusted OR, 1.00; 95% CI, 1.00-1.01) were significantly associated with the highest tertile of the average size of the choriocapillaris. Choriocapillaris flow void features measured using OCTA were associated with cardiovascular risk profiles in patients with AMI. OCTA may be used as an indicator of cardiovascular risk profiles and could improve cardiovascular risk assessments.

Comparison between Deep-Learning-Based Ultra-Wide-Field Fundus Imaging and True-Colour Confocal Scanning for Diagnosing Glaucoma.

In this retrospective, comparative study, we evaluated and compared the performance of two confocal imaging modalities in detecting glaucoma based on a deep learning (DL) classifier: ultra-wide-field (UWF) fundus imaging and true-colour confocal scanning. A total of 777 eyes, including 273 normal control eyes and 504 glaucomatous eyes, were tested. A convolutional neural network was used for each true-colour confocal scan (Eidon AF™, CenterVue, Padova, Italy) and UWF fundus image (Optomap™, Optos PLC, Dunfermline, UK) to detect glaucoma. The diagnostic model was trained using 545 training and 232 test images. The presence of glaucoma was determined, and the accuracy and area under the receiver operating characteristic curve (AUC) metrics were assessed for diagnostic power comparison. DL-based UWF fundus imaging achieved an AUC of 0.904 (95% confidence interval (CI): 0.861−0.937) and accuracy of 83.62%. In contrast, DL-based true-colour confocal scanning achieved an AUC of 0.868 (95% CI: 0.824−0.912) and accuracy of 81.46%. Both DL-based confocal imaging modalities showed no significant differences in their ability to diagnose glaucoma (p = 0.135) and were comparable to the traditional optical coherence tomography parameter-based methods (all p > 0.005). Therefore, using a DL-based algorithm on true-colour confocal scanning and UWF fundus imaging, we confirmed that both confocal fundus imaging techniques had high value in diagnosing glaucoma.

Severe Retinopathy of Prematurity Associated With Neurodevelopmental Disorder in Children.

OBJECTIVE: This study aimed to investigate whether severe retinopathy of prematurity (ROP) could be an association factor for neurodevelopmental disorders in premature infants without other risk factors-such as congenital anomalies, birth injuries, and neurological diseases-that may cause developmental delay. METHODS: We used health claims data recorded between 2007 and 2018 in the Korean National Health Insurance Service (KNHIS) database. We recruited a total of 18,256 premature infant born between 2007 and 2008 without congenital anomaly or birth injury (with ROP 6,995, without ROP 11,261) and divided them into four groups as follows: Group A, 209 extremely premature infants [gestational age (GA) < 28] with mild ROP; Group B, 75 extremely premature infants (GA < 28) with severe ROP; Group C, 6,510 other premature infants (28 ≤ GA <37)with mild ROP; and Group D, 201 other premature infants (28 ≤ GA < 37) with severe ROP. Using regression analysis, we analyzed whether there was a correlation between ROP prevalence, severity, and developmental delay in premature infants without other risk factors. RESULTS: The prevalence of developmental delay, according to GA and ROP severity, was higher in patients with severe ROP than in the other patients. The prevalence gradually decreased after birth. Among extremely premature infants with ROP, those with severe ROP had a 3.082-fold higher association with neurodevelopmental complications than those with mild ROP (p < 0.001). Compared with other premature infants with ROP, those with severe ROP had a 3.269-fold higher association with neurodevelopmental complications than those with mild ROP. CONCLUSION: The severity of ROP may be associated with neurodevelopmental disorders in premature infants.

Swept-Source OCT Angiography Features in Patients after Macular Hole Surgery.

This study aimed to compare findings of optical coherence tomography (OCT) angiography (OCTA) between eyes with nearly recovered and partially recovered outer retina after full-thickness macular hole (FTMH) surgery and to identify OCTA findings associated with visual acuity. We retrospectively reviewed 30 patients who underwent surgery for idiopathic FTMH. Swept-source OCT (SS-OCT) and OCTA were performed preoperatively and at three and six months postoperatively. Subgroups were divided according to the integrity of the external limiting membranes and ellipsoid zones postoperatively. Correlations of best-corrected visual acuity six months postoperatively with SS-OCT and OCTA measurements were analyzed. There was no difference in preoperative retinal or choroidal vascular index on OCTA between the nearly and partially recovered groups. Six months postoperatively, the choriocapillaris flow-void area was significantly higher in the partially recovered group than in the fellow eye. The nearly recovered group showed better choroidal vascular flow, and vision at six months postoperatively correlated with the ratio of the operated eye's choriocapillaris flow-void area to the fellow eye. Sufficient choriocapillaris flow on OCTA is associated with better outer retinal recovery and visual outcomes after macular hole surgery.

Analysis of MicroRNA Expression in Tears of Patients with Herpes Epithelial Keratitis: A Preliminary Study.

Purpose: Herpes epithelial keratitis (HEK) is the most common form of herpes simplex virus (HSV) eye involvement, and understanding the molecular mechanisms underlying HEK is important. We investigated the expression of microRNAs (miRNAs) in the tears of patients with HEK. Methods: Tear samples from eight patients with HEK and seven age-matched controls were evaluated. Clinical ophthalmologic evaluation was performed, and an anterior segment photograph was obtained after fluorescence staining. Dendritic or geographic ulcer areas were measured using ImageJ software. The expression of 43 different miRNAs in tears was measured using real-time polymerase chain reaction and compared between patients with HEK and controls. Differences in miRNA expression between the dendritic and geographic ulcer groups and correlations involving miRNA expression and ulcer area were evaluated. Results: Of the 43 miRNAs, 23 were upregulated in patients with HEK compared to normal controls. MiR-15b-5p, miR-16-5p, miR-20b-5p, miR-21-5p, miR-23b-3p, miR-25-3p, miR-29a-3p, miR-30a-3p, miR-30d-5p, miR-92a-3p, miR-124-3p, miR-127-3p, miR-132-3p, miR-142-3p, miR-145-5p, miR-146a-5p, miR-146b-5p, miR-155-5p, miR-182-5p, miR-183-5p, miR-221-3p, miR-223-3p, and miR-338-5p were significantly upregulated in patients with HEK. MiR-29a-3p exhibited significant differences between the dendritic and geographic ulcer groups. All 23 miRNAs with significant differences between patients with HEK and the control group were not significantly correlated with ulcer area. Conclusions: Twenty-three miRNAs were significantly upregulated in the tears of patients with HEK, and the expression of miRNAs may play important roles in herpes infection in relation to host immunity.

Differential expression of aqueous humor microRNAs in central retinal vein occlusion and its association with matrix metalloproteinases: a pilot study.

The aim of this study is to investigate the differential expression of microRNAs (miRNAs) in the aqueous humor (AH) of patients with central retinal vein occlusion (CRVO), and their association with AH matrix metalloproteinase (MMP) activity. Eighteen subjects, including 10 treatment naïve patients with CRVO and 8 control subjects, scheduled for intravitreal injection and cataract surgery, respectively, were included. AH samples were collected at the beginning of the procedure. A microarray composed of 84 miRNAs was performed to identify differentially expressed miRNAs in CRVO AH, which were further analyzed using bioinformatic tools to identify directly related cytokines/proteins. Eight miRNAs (hsa-mir-16-5p, hsa-mir-142-3p, hsa-mir-19a-3p, hsa-mir-144-3p, hsa-mir-195-5p, hsa-mir-17-5p, hsa-mir-93-5p, and hsa-mir-20a-5p) were significantly downregulated in the CRVO group. Bioinformatic analysis revealed a direct relationship among downregulated miRNAs, CRVO, and the following proteins: MMP-2, MMP-9, tumor necrosis factor, transforming growth factor beta-1, caspase-3, interleukin-6, interferon gamma, and interleukin-1-beta. Activities of MMP-2 and -9 in AH were detected using gelatin zymography, showing significant increase in the CRVO group compared to the control group (p < 0.01). This pilot study first revealed that MMP-2 and -9 were directly related to downregulated miRNAs and showed significant increase in activity in AH of patients with CRVO. Therefore, the relevant miRNAs and MMPs in AH could serve as potential biomarkers or therapeutic targets for CRVO.

Ophthalmic complications in retinopathy of prematurity in the first decade of life in Korea using the national health insurance database.

The aim of this study is to investigate the epidemiology of ophthalmic complications of retinopathy of prematurity (ROP) after preterm birth using population-based database in South Korea. Using the National Health Insurance database, ophthalmic complications among premature infants born in 2007-2008 during their 10-year follow-up period were identified. Annual cumulative incidence rate and period prevalence of complications at each age were analyzed among those with ROP and those who underwent treatment for ROP (tROP). The hazard ratios (HRs) according to the presence of ROP and treatment for ROP were also analyzed. We identified 18,256 premature infants, 6995 of whom had ROP. The prevalence at 10th year for overall ophthalmic complications was 11.1% and 35.9% among ROP and tROP, respectively. Strabismus, amblyopia, and glaucoma were the three most common complications. The presence of ROP was associated with higher risk of complications (HR 1.53, 95%CI 1.44-1.61) among premature infants, and the presence of treatment for ROP was associated with higher risk of complications (HR 4.31, 95%CI 3.74-4.98) among ROP cases. This study reports the nationwide epidemiologic data on ophthalmic complications of ROP during the first decade of life, which will help advance our understandings and establish national strategies in managing ROP.