Therapeutic Efficacy of Intravitreal Conbercept Injections with or without Focal Macular Photocoagulation for Diabetic Macular Edema.

Objective: This study aimed to investigate the effectiveness and safety of intravitreal conbercept injections with or without focal macular photocoagulation in the treatment of diabetic macular edema (DME). Methods: This retrospective study included 60 DME patients (60 eyes) divided into two treatment groups. The conbercept group received monthly intravitreal injections for 5 consecutive sessions, while the combination therapy group received intravitreal injections and focal macular photocoagulation. Changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT) were observed before and at months 1, 3, 6, 9, and 12 after treatment in both groups, along with the number of intravitreal conbercept injections administered. Results: At 1, 3, 6, 9, and 12 months after treatment, both the conbercept and combined treatment groups showed improvement in best-corrected visual acuity (BCVA) and decrease in central macular thickness (CMT) compared to before treatment, with statistical significant differences (P < .05). However, the differences in BCVA and CMT between the two groups at each time point after treatment were not significant (P > .05). During the 1-year follow-up period, the mean number of injections in the combined treatment group was 6.3±0.8, which was less than that in the conbercept treatment group (7.6 ± 0.9), with a significant difference (t = 5.556, P < .001). The incidence of subconjunctival hemorrhage was 10.9% and 10.5% in the two groups, respectively, with no significant inter-group difference (χ² = 0.013, P = .908). None of the patients exhibited serious treatment-related ocular and systemic complications during the treatment period. Conclusions: Treatment of DME with intravitreal conbercept injections, whether with or without focal macular photocoagulation, is safe and effective in improving the patients' visual acuity and retinal anatomy. However, patients who receive combined treatment require fewer intravitreal injections than those who receive conbercept treatment alone.

Rituximab, Intravitreal Bevacizumab and Laser Photocoagulation for Treatment of Macrophage Activation Syndrome and Retinal Vasculitis in Lupus: A Case Report.

Systemic lupus erythematosus (SLE) most commonly manifests as mild to moderate disease with severe manifestations such as diffuse alveolar hemorrhage, central nervous system vasculitis, macrophage activation syndrome (MAS) or retinal vasculitis (RV) with visual disturbances occurring in a significantly smaller proportion of patients, most of whom have a poor outcome. Macrophage activation syndrome and RV are insufficiently early and rarely recognized presentations of lupus-consequently there are still no treatment recommendations. Here we present the course of diagnosis and treatment of a patient with an SLE flare that resulted in both life-threatening disease (MAS) and vision-threatening disease (RV). The patient was successfully treated with systemic immunosuppressives, a high dose of glucocorticoids and rituximab (RTX), in parallel with intraocular therapy, intravitreal bevacizumab (BEV) and laser photocoagulation.

Photocoagulation with GREENLIGHT© laser in radiation-induced haemorrhagic cystitis: Results of a single-center series.

INTRODUCTION: Radiation-induced haemorrhagic cystitis (RIHC) is one complication of the pelvic radiotherapy. The GREENLIGHT© laser (GL) has been barely studied in the treatment of radiation cystitis. The primary objective was to evaluate the efficacy of GL in refractory RIHC patients (RRC) in a single-centre series. MATERIALS AND METHODS: Twenty-nine patients were treated by GL bladder photocoagulation (GLBP). These patients showed signs of refractory haematuria in the context of RIHC. The primary endpoint was the absence of haematuria that would require a subsequent surgical intervention. Secondary endpoints were postoperative hospitalization length of stay, the occurrence of complications according to the Clavien-Dindo classification, the occurrence of functional urinary disorders and the number of cystectomies. RESULTS: After a median follow-up of 30 months, 24 (82.7%) patients had no recurrence of haematuria. No postoperative complications were reported. A disabling overactive bladder secondary to the procedure occurred in 9 patients (31.0%). Two patients needed a cystectomy at 1 and 11 months. CONCLUSION: GLBP may constitute an efficient line of treatment for RIHC. Despite overactive bladder it allowed to avoid or delay cystectomy.

Efficacy of Ahmed Glaucoma Valve Implantation on Neovascular Glaucoma.

To evaluate the efficacy of Ahmed glaucoma valve (AGV) implantation in treating neovascular glaucoma (NVG) and analyze the factors influencing the surgical success rate, a retrospective investigation of 59 NVG patients (66 eyes) who underwent AGV implantation was conducted at Jiangsu Province Hospital, China, from January 2014 to June 2018. Intraocular pressure (IOP), visual acuity, surgical success rates, medications, and complications were monitored at post-operative 1 day, 1 week, 1, 3, 6 and 12 months. Surgical success criteria were defined as 6 mm Hg < IOP < 21 mmHg with or without additional medications. Results showed average IOP was statistically significant between pre-operative visit and each follow-up visit (all P<0.05). At 12 months, the success rate was 66.7%. Multiple stepwise regression analysis suggested that age, panretinal photocoagulation (PRP), complications and hyphema were significant factors influencing the surgical success rate (all P<0.05). Thus, we conclude that AGV implantation is effective and safe for treatment of NVG. Surgical success is dependent on age, PRP, complications, and hyphema.

Congenital Laser-Induced Burns: A Potential Complication after Laser Photocoagulation in Monochorionic Twin Pregnancy.

Background: Fetoscopic laser photocoagulation can directly injure fetal skin and may at birth resemble aplasia cutis congenita (ACC). Case report: A twin monochorionic pregnancy was complicated by twin-to-twin transfusion syndrome requiring in utero laser photocoagulation, resulting in the death of one twin. After birth, the viable baby presented skin lesions in both legs that were congruent with laser-induced burns. Conclusions: Laser-induced burns present as asymmetric superficial non-necrotic or ulcerated lesions, with a geographic outline, which turn into scars with no retraction or contractures and no changes in pain perception or motor limitations over time. ACC lesions are bilateral and symmetric, with a regular outline, an ulcerated or necrotic appearance, a higher degree of skin involvement affecting all skin layers and, over time, they turn into scars with retraction and contractures. These differential features may help clinicians in a challenging approach to the diagnosis of congenital skin defects.

Inhibition of YAP ameliorates choroidal neovascularization via inhibiting endothelial cell proliferation.

Purpose: Age-related macular degeneration (AMD) is the leading cause of central visual loss among patients over the age of 55 years worldwide. Neovascular-type AMD (nAMD) accounts for approximately 10% of patients with AMD and is characterized by choroidal neovascularization (CNV). The proliferation of choroidal endothelial cells (CECs) is one important step in the formation of new vessels. Transcriptional coactivator Yes-associated protein (YAP) can promote the proliferation of multiple cancer cells, corneal endothelial cells, and vascular smooth muscle cells, which participate in angiogenesis. This study intends to reveal the expression and functions of YAP during the CNV process. Methods: In the study, a mouse CNV model was generated by laser photocoagulation. YAP expression was detected with western blotting and immunohistochemistry. YAP siRNA and ranibizumab, a VEGF monoclonal antibody, were injected intravitreally in CNV mice. The YAP and VEGF expression levels after injection were detected with western blotting. The incidence and leakage area of CNV were measured with fundus fluorescein angiography, choroidal flat mounting, and hematoxylin and eosin (HE) staining. Immunofluorescent double staining was used to detect YAP cellular localization with CD31 (an endothelial cell marker) antibody. Proliferating cell nuclear antigen (PCNA) expression in CNV mice without or with YAP siRNA intravitreal injection and the colocalization of PCNA and CD31 were measured with western blotting and immunofluorescent double staining, respectively. Results: YAP expression increased following laser exposure, in accordance with vascular endothelial growth factor (VEGF) expression. YAP siRNA and ranibizumab decreased VEGF expression and the incidence and leakage area of CNV. YAP was localized in the vascular endothelium within the CNV site. Additionally, after laser exposure, YAP siRNA inhibited the increased expression of PCNA, which was colocalized with endothelial cells. Conclusions: This study showed that YAP upregulation promoted CNV formation by upregulating the proliferation of endothelial cells, providing evidence for the molecular mechanisms of CNV and suggesting a novel molecular target for nAMD treatment.

[A Case Report of Mirror Syndrome after Fetoscopic Laser Photocoagulation for Twin to Twin Transfusion Syndrome].

Mirror syndrome is a rare obstetric condition where a mother "mirrors" the edema of her hydropic fetus and placenta. We present the successful resolution of mirror syndrome following fetoscopic laser photocoag- ulation for twin to twin transfusion syndrome (TTTS). A 36-year-old woman was pregnant with monocho- rionic twins. She was diagnosed with TTTS at the 23rd week of pregnancy and transported to our hospi- tal by ambulance for treatment Her human chorionic gonadotropin serum concentration was 144,437 IU - ml'. Fetoscopic laser photocoagulation was performed under local anesthesia with dexmedetomidine. How- ever, her restlessness disturbed the procedure and conversion to general anesthesia was required, which facilitated successful completion of the surgical proce- dure. Postoperatively, her vital signs were stable, and after 30 min, the saturation decreased to 80%. She was intubated, sedated with propofol, and transported to the intensive care unit A transthoracic ultrasound examination showed no cardiomyopathy. A chest X-ray suggested pulmonary edema. Pulmonary edema disap- peared immediately, and she was extubated after 36 hr. Postoperatively, the twins had a good prognosis. There are several reports of mirror syndrome after fetoscopic laser photocoagulation for TTTS. Recovery from mirror syndrome can improve following the reso- lution of fetal hydrops in TTTS using fetoscopic laser photocoagulation.

Retinal fibrosis in diabetic retinopathy.

In response to injury, reparative processes are triggered to restore the damaged tissue; however, such processes are not always successful in rebuilding the original state. The formation of fibrous connective tissue is known as fibrosis, a hallmark of the reparative process. For fibrosis to be successful, delicately balanced cellular events involving cell proliferation, cell migration, and extracellular matrix (ECM) remodeling must occur in a highly orchestrated manner. While successful repair may result in a fibrous scar, this often restores structural stability and functionality to the injured tissue. However, depending on the functionality of the injured tissue, a fibrotic scar can have a devastating effect. For example, in the retina, fibrotic scarring may compromise vision and ultimately lead to blindness. In this review, we discuss some of the retinal fibrotic complications and highlight mechanisms underlying the development of retinal fibrosis in diabetic retinopathy.

Pseudoamniotic Band Syndrome after In Utero Intervention for Twin-to-Twin Transfusion Syndrome: Case Reports and Literature Review.

Pseudoamniotic band syndrome (PABS) is a rare iatrogenic complication that arises after invasive procedures in monochorionic twins. We report 3 cases of PABS, 2 after fetoscopic laser photocoagulation and 1 after bipolar cord coagulation. Two cases were detected antenatally by ultrasound; out of the two, one underwent successful fetoscopic release of amniotic band, which is the first report in twin pregnancy to our knowledge. In our centre, the incidence of PABS was found to be 2%. There were 25 cases of PABS reported previously, of which 12 cases with clinical details were reviewed together with our 3 cases. The fetal limbs were involved in all 15 cases, leading to constriction or amputation. The umbilical cord was involved in 2 cases, resulting in fetal death in one and pregnancy termination in the other. Antenatal detection of PABS is rare (27%; 4/15) as this requires a high index of suspicion. Serial postoperative targeted ultrasound surveillance of the fetal limbs and umbilical cord is necessary, particularly when features of septostomy or chorioamniotic membrane separation are found. Colour Doppler examination for the perfusion of the affected limb should be performed when PABS is detected. Fetoscopic release of amniotic band could salvage the fetal limb from amputation when impaired blood flow is detected.

Panretinal Photocoagulation vs Intravitreous Ranibizumab for Proliferative Diabetic Retinopathy: A Randomized Clinical Trial.

IMPORTANCE: Panretinal photocoagulation (PRP) is the standard treatment for reducing severe visual loss from proliferative diabetic retinopathy. However, PRP can damage the retina, resulting in peripheral vision loss or worsening diabetic macular edema (DME). OBJECTIVE: To evaluate the noninferiority of intravitreous ranibizumab compared with PRP for visual acuity outcomes in patients with proliferative diabetic retinopathy. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial conducted at 55 US sites among 305 adults with proliferative diabetic retinopathy enrolled between February and December 2012 (mean age, 52 years; 44% female; 52% white). Both eyes were enrolled for 89 participants (1 eye to each study group), with a total of 394 study eyes. The final 2-year visit was completed in January 2015. INTERVENTIONS: Individual eyes were randomly assigned to receive PRP treatment, completed in 1 to 3 visits (n = 203 eyes), or ranibizumab, 0.5 mg, by intravitreous injection at baseline and as frequently as every 4 weeks based on a structured re-treatment protocol (n = 191 eyes). Eyes in both treatment groups could receive ranibizumab for DME. MAIN OUTCOMES AND MEASURES: The primary outcome was mean visual acuity change at 2 years (5-letter noninferiority margin; intention-to-treat analysis). Secondary outcomes included visual acuity area under the curve, peripheral visual field loss, vitrectomy, DME development, and retinal neovascularization. RESULTS: Mean visual acuity letter improvement at 2 years was +2.8 in the ranibizumab group vs +0.2 in the PRP group (difference, +2.2; 95% CI, -0.5 to +5.0; P < .001 for noninferiority). The mean treatment group difference in visual acuity area under the curve over 2 years was +4.2 (95% CI, +3.0 to +5.4; P < .001). Mean peripheral visual field sensitivity loss was worse (-23 dB vs -422 dB; difference, 372 dB; 95% CI, 213-531 dB; P < .001), vitrectomy was more frequent (15% vs 4%; difference, 9%; 95% CI, 4%-15%; P < .001), and DME development was more frequent (28% vs 9%; difference, 19%; 95% CI, 10%-28%; P < .001) in the PRP group vs the ranibizumab group, respectively. Eyes without active or regressed neovascularization at 2 years were not significantly different (35% in the ranibizumab group vs 30% in the PRP group; difference, 3%; 95% CI, -7% to 12%; P = .58). One eye in the ranibizumab group developed endophthalmitis. No significant differences between groups in rates of major cardiovascular events were identified. CONCLUSIONS AND RELEVANCE: Among eyes with proliferative diabetic retinopathy, treatment with ranibizumab resulted in visual acuity that was noninferior to (not worse than) PRP treatment at 2 years. Although longer-term follow-up is needed, ranibizumab may be a reasonable treatment alternative, at least through 2 years, for patients with proliferative diabetic retinopathy. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01489189.

Roles of NFκB-miR-29s-MMP-2 circuitry in experimental choroidal neovascularization.

BACKGROUND: Previous reports have indicated that matrix metallopeptidase-2 (MMP-2) regulates angiogenic processes, which are involved in choroidal neovascularization (CNV). However, the regulation of MMP-2 in CNV has not been well-characterized. To gain more information about the regulation of MMP-2 in CNV, we analyzed the circuitry associated with MMP-2 regulation in a CNV model and in cell cultures, focusing on NFκB and the microRNA-29 family (miR-29s). METHODS: The CNV model was established by subjecting C57BL/6 mice to fundus photocoagulation with a krypton red laser. In choroidal-retinal pigment epithelial (RPE) tissues of the model, immunohistochemistry was used to evaluate the angiogenesis and MMP-2 expression; reverse-transcription quantitative PCR (RT-qPCR) was used to determine the levels of miR-29s; and western blot was used to analyze the protein levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) inhibitor, IκBα, and its phosphorylated form, phospho-IκBα. At the cellular level, RT-qPCR was used to examine the levels of miR-29s following NFκB activation by tumor necrosis factor alpha (TNFα); and western blot and luciferase assay were used to determine the regulation of MMP-2 by miR-29s in a human RPE cell line (ARPE-19) and in an umbilical vein endothelial cell line (EA hy926). RESULTS: MMP-2 staining was increased in the choroidal neovascular membrane of laser-treated retina. Also, the NFκB pathway was induced in choroid-RPE tissue, as evidenced by a lower protein level of IκBα and a higher level of phospho-IκBα in the tissue homogenates than in those from non-treated eyes. During the period when the NFκB pathway was induced, reduced miR-29s were detected in the choroidal-RPE tissue of the laser-treated eyes. In cultured ARPE-19 cells, TNFα decreased miR-29a, b, and c, and the effects were rescued by NFκB decoy. In ARPE-19 and EA hy926, miR-29s mimics reduced the contents of secreted MMP-2 in the culture media. We also documented that miR-29s reduced MMP-2 3'-UTR-mediated luciferase transcription. CONCLUSIONS: The results suggest that in CNV, NFκB activation inhibits miR-29s, which may contribute to angiogenesis by up-regulating the MMP-2 protein level in RPE cells. These observations may help in developing a strategy for resolving CNV by targeting miR-29s levels.

A long-term follow-up of patients with retinopathy of prematurity treated with photocoagulation and cryotherapy.

To evaluate the refractive characteristics of adults diagnosed with retinopathy of prematurity (ROP) treated with ablation treatment as children, we measured best corrected visual acuity (BCVA, logMAR), spherical equivalent refraction (SER), axial length (AL), lens thickness (LT), anterior chamber depth (ACD) and the corneal curvature radius (CCR) from 46 eyes, 24 patients (15-30 years old) that were diagnosed with ROP. Patients were divided into two groups dependent on the size of the treated retina at the time of ablation treatment; i.e., 360 degrees group (treatment over the whole circumference of the retina; n = 18) and partial group (treatment over part of the retina; n = 28). The study showed that LT was significantly larger (P < 1x10(-4)) and ACD was significantly shorter (P < 1 x 10(-3)) in 360 degrees group (4.26 +/- 0.40 mm and 2.92 +/- 0.48 mm, respectively) than those in partial group (3.71 +/- 0.34 mm and 3.42 +/- 0.26 mm, respectively). However, there were no differences in SER (-6.52 +/- 3.54 diopter vs. -5.95 +/- 4.12 diopter, P = 0.31), AL (23.9 +/- 1.42 mm vs. 25.0 +/- 21.48 mm, P = 0.08) and CCR (7.59 +/- 0.37 mm vs. 7.59 +/- 0.19 mm, P = 0.86). These results indicated that the eyes in the 360 degrees group had larger LTs but did not have extended ALs compared with the partial group.

Risk factor analysis for long-term unfavorable ocular outcomes in children treated for retinopathy of prematurity.

The aim in this study was to report long-term ocular outcomes of neonates treated for retinopathy of prematurity (ROP) and potential risk factors for unfavorable ocular outcomes. The study consisted of neonates treated for ROP between March 1999 and November 2009. Data relating baseline characteristics and late structural, functional and refractive ocular outcomes were recorded. The association between the unfavorable ocular outcomes and ROP-related risk factors was evaluated by regression analysis. Forty-eight children were included for assessment. Average chronological age at the time of followup was 3.11±0.73 years. The rates of unfavorable structural and functional outcomes were 12% and 15.3%, respectively. Ocular deviation was common (27.1%), and mostly esotropic (12/13). A clear myopic tendency was observed (51.2%), and the mean spherical equivalent per eye was -0.72±2.9 diopters. Regression analyses for unfavorable ocular outcomes revealed intraventricular hemorrhage as a core independent risk factor. In conclusion, ROP treatment has shown promising results in both structure and function. Because of the high risk of developing an unfavorable outcome, a more intense follow-up is required in neonates with a history of intraventricular hemorrhage in the neonatal period. Further studies from other centers are needed to develop a national database, which may validate this observation.

Photocoagulation Up to Ora Serrata in Diabetic Vitrectomy to Prevent Recurrent Vitreous Hemorrhage.

PURPOSE: To evaluate the role of performing photocoagulation up to ora serrata during vitrectomy in preventing recurrent vitreous hemorrhage (VH) in patients undergoing pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR). METHODS: This retrospective, nonrandomized study included 60 eyes from 60 patients who had undergone PPV for VH due to PDR. These patients were divided into two groups: group 1, those who underwent photocoagulation up to ora serrata using the scleral indentation technique during surgery; and group 2, those who did not undergo scleral indentation when photocoagulation and underwent photocoagulation up to vortex veins. Their hospital records were analyzed to investigate the recurrence rate of VH, the time until recurrence of VH after surgery, logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) measured before surgery and at 1, 2, and 3 years after surgery, and the occurrence of complications such as neovascular glaucoma (NVG) during follow-up. RESULTS: Group 1 exhibited lower recurrence rate of VH (2 of 30 [6.7%] vs. 10 of 30 [33.3%], p = 0.01) and lower occurrence of postoperative NVG (2 of 30 [6.7%] vs. 8 of 30 [26.7%], p = 0.038) compared with group 2. There were no statistically significant differences in logMAR BCVA measured at 1, 2, and 3 years between the two groups (at 1 year: 0.54 ± 0.43 vs. 0.54 ± 0.44, p = 0.954; at 2 years: 0.48 ± 0.47 vs. 0.55 ± 0.64, p = 0.235; at 3 years: 0.51 ± 0.50 vs. 0.61 ± 0.77, p = 0.200). Logistic regression analysis showed that among several factors that could affect recurrence rate of VH, only range of photocoagulation performed was a statistically significant factor (odds ratio, 0.119; 95% confidence interval, 0.022-0.659; p = 0.015). CONCLUSIONS: Photocoagulation treatment over a wider range with scleral indentation could be a beneficial adjunct procedure for preventing postoperative recurrent VH following diabetic vitrectomy.

The neurological outcomes of surviving twins in severe twin-twin transfusion syndrome treated by fetoscopic laser photocoagulation at a newly established center.

OBJECTIVE: To evaluate the incidence and predictive factors of poor neurological outcome in survivors of twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic laser photocoagulation (FLP). METHODS: Brain magnetic resonance imaging (MRI) and neurodevelopmental assessment were performed at a corrected age of 1 year in survivors of TTTS treated by FLP. Severe neurological abnormality was defined as either the presence of severe clinical neurodevelopmental disability or severe anomalies, visualized on MRI of the brain. RESULT: In a consecutive series of 46 cases treated by FLP, the total survival rate was 66.3%; survival of at least one was 80.4%. Severe neurodevelopment disability was 6.7 % (4/59) and the presence of a severe anomaly on brain imaging was 8.8% (5/57), which combined to a clinical or MRI abnormality rate of 10.5% (6/57). Univariate analysis revealed that early gestational age at delivery was the most significant predictor. However, the multiple logistic regression model did not identify any significant variables. CONCLUSION: In this small series, we determined a rate of clinical neurologic impairment rate at the age of 1 year of 6.7%, which compares to what has been published.

Limb constriction secondary to pseudoamniotic band syndrome after selective fetoscopic laser surgery: report of a case with a favorable outcome.

Pseudoamniotic band syndrome (PABS) is an iatrogenic complication that causes entanglement of fetal parts in a constrictive sheet of detached or ruptured amniotic membrane after an invasive procedure, namely amniocentesis, amnioreduction or septostomy in twins. The incidence and risk factors for PABS after fetoscopy-guided laser have not been documented [Winer et al.: Am J Obstet Gynecol 2008;198:393.e1-393.e5]. We report a case of monochorionic biamniotic twin pregnancy submitted to selective fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome at 16 weeks of gestation. The procedure was complicated by the death of one of the fetuses at 24 weeks of gestation. Moreover, the surviving twin was diagnosed postnatally with pseudoamniotic band syndrome, presenting with affected limbs. The newborn was submitted to surgical correction of these lesions with a successful outcome and was discharged on day 15.

Comparison of Pregnancy Outcomes of Previable and Periviable Rupture of Membranes After Laser Photocoagulation for Twin-Twin Transfusion Syndrome.

OBJECTIVE: To describe the pregnancy outcomes of patients who experienced previable and periviable prelabor rupture of membranes (PROM) after the treatment of twin-twin transfusion syndrome. METHODS: We conducted a retrospective cohort study of patients whose pregnancies were complicated by twin-twin transfusion syndrome who were treated with fetoscopic laser photocoagulation at a single fetal center and subsequently experienced PROM from April 2010 to June 2019. Outcomes were infant survival and latency from PROM to delivery. Patients were grouped by gestational age at PROM (before 26 weeks of gestation and 26 weeks or later). The group with PROM before 26 weeks of gestation was stratified by gestational age at PROM for further description of outcomes. RESULTS: Two-hundred fifty of 653 patients (38%) developed PROM, 81 before 26 weeks of gestation and 169 after 26 weeks of gestation. In the setting of PROM before 26 weeks of gestation, the rate of survival of both twins to neonatal intensive care unit (NICU) discharge was 46.3%, compared with 76.9% in the setting of PROM at 26 weeks of gestation or later ( P <.001); the survival rate of at least one twin was 61.2% and 98.5%, respectively ( P <.001). Fourteen, 22, and 45 patients experienced PROM at 16-19 6/7, 20-22 6/7, and 23-25 6/7 weeks of gestation, respectively. Survival of both twins and at least one twin to NICU discharge was 25.0%, 47.4%, 52.8% (for two) and 33.3%, 47.4%, and 77.8% (for at least one), respectively, among those groups. Fifty-seven of the 81 patients with PROM before 26 weeks of gestation experienced a latency longer than 48 hours. In the setting of PROM before 26 weeks of gestation, when latency lasted longer than 48 hours, overall survival was improved (69.6% vs 53.7%, respectively, P =.017). With latency longer than 48 hours and PROM at 16-19 6/7, 20-22 6/7, and 23-25 6/7 weeks of gestation, survival of both twins to NICU discharge was 60.0%, 61.5%, and 60.7%, respectively, and survival of at least one twin was 80.0%, 61.5%, and 85.7%, respectively. CONCLUSION: Earlier gestational age at PROM after laser photocoagulation is associated with longer latency but lower rates of survival. When PROM occurs before 26 weeks of gestation and latency exceeds 48 hours, rates of neonatal survival are significantly improved.

Novel serum proteomic signatures in a non-human primate model of retinal injury.

PURPOSE: To identify candidate protein biomarkers in sera indicative of acute retinal injury. METHODS: We used laser photocoagulation as a model of acute retinal injury in Rhesus macaques. In a paired-control study design, we collected serum from each animal (n=6) at 4 h, 1 day, and 3 days following a mock procedure and then again following retinal laser treatment that produced mild lesions. Samples were fractionated by isoelectric focusing, digested with trypsin, and analyzed by liquid chromatography/tandem mass spectrometry (LC-MS/MS). Spectral counting was used to determine relative protein abundances and identify proteins with statistically significant differences between control and treated sera. RESULTS: Mild retinal injury was confirmed by fundus photography and histological examination. The average number of total proteins detected by LC-MS/MS was 908±82 among samples from all three time points. Following statistical analysis and employing stringent filtering criteria, a total of 19 proteins were identified as being significantly more abundant in sera following laser-induced retinal injury, relative to control sera. Many of the proteins detected were unique to one time point. However, four proteins (phosphoglycerate kinase 1, keratin 18, Lewis alpha-3-fucosyltransferase, and ephrin receptor A2) showed differences that were significant at both 4 h and 1 day after laser treatment, followed by a decrease to baseline levels by day 3. CONCLUSIONS: A serum biomarker response to mild retinal laser injury was demonstrated in a primate model. Among the proteins detected with highest significant differences, most are upregulated within 24 h, and their appearance in the serum is transient. It is conceivable that a panel of these proteins could provide a means for detecting the acute-phase response to retinal injury. Further investigation of these candidate biomarkers and their correlation to retinal damage is warranted.

Application of 5G Technology to Conduct Real-Time Teleretinal Laser Photocoagulation for the Treatment of Diabetic Retinopathy.

Importance: Interest in teleophthalmology has been growing, especially during the COVID-19 pandemic. The advent of fifth-generation (5G) wireless systems has the potential to revolutionize teleophthalmology, but these systems have not previously been leveraged to conduct therapeutic telemedicine in the ophthalmology field. Objective: To assess the feasibility of 5G real-time laser photocoagulation as a telemedicine-based treatment for diabetic retinopathy (DR). Design, Setting, and Participants: This was a prospective study involving a retinal specialist from the Peking Union Medical College Hospital in Beijing, China, who performed online 5G real-time navigated retinal laser photocoagulation to treat participants with proliferative or severe nonproliferative DR who had been recruited in the Huzhou First People's Hospital in Zhejiang Province, China, located 1200 km from Beijing from October 2019 to July 2020. Interventions: These teleretinal DR and laser management procedures were conducted using a teleophthalmology platform that used the videoconference platform for teleconsultation, after which telelaser planning and intervention were conducted with a laser system and a platform for remote computer control, which were connected via 5G networks. Main Outcomes and Measures: Diabetic eye prognosis and the real-time laser therapy transmission speed were evaluated. Results: A total of 6 participants (9 eyes) were included. Six eyes were treated via panretinal photocoagulation alone, while 1 eye underwent focal/grid photocoagulation and 2 eyes underwent both panretinal photocoagulation and focal/grid photocoagulation. The mean (SD) age was 53.7 (13.6) years (range, 32-67 years). The mean (SD) duration of diabetes was 14.3 (6.4) years (range, 3-20 years). The mean (SD) logMAR at baseline was 0.32 (0.20) (20/30 Snellen equivalent). Retinal telephotocoagulation operations were performed on all eyes without any noticeable delay during treatment. The mean (SD) number of panretinal photocoagulation laser spots per eye in 1 session was 913 (243). Conclusions and Relevance: This study introduces a novel teleophthalmology paradigm to treat DR at a distance. Applying novel technologies may continue to ensure that remote patients with DR and other conditions have access to essential health care. Further studies will be needed to compare this approach with the current standard of care to determine whether visual acuity or safety outcomes differ.

Risk factors associated with progression of diabetic retinopathy in eyes treated with panretinal photocoagulation.

Uncontrolled diabetes has been associated with progression of diabetic retinopathy (DR) in several studies. Therefore, we aimed to investigate systemic and ophthalmic factors related to worsening of DR even after completion of panretinal photocoagulation (PRP). We retrospectively reviewed DR patients who had completed PRP in at least one eye with a 3-year follow-up. A total of 243 eyes of 243 subjects (mean age 52.6 ± 11.6 years) were enrolled. Among them, 52 patients (21.4%) showed progression of DR after PRP (progression group), and the other 191 (78.6%) patients had stable DR (non-progression group). The progression group had higher proportion of proliferative DR (P = 0.019); lower baseline visual acuity (P < 0.001); and higher platelet count (P = 0.048), hemoglobin (P = 0.044), and hematocrit, (P = 0.042) than the non-progression group. In the multivariate logistic regression analysis for progression of DR, baseline visual acuity (HR: 0.053, P < 0.001) and platelet count (HR: 1.215, P = 0.031) were identified as risk factors for progression. Consequently, we propose that patients with low visual acuity or high platelet count are more likely to have progressive DR despite PRP and require careful observation. Also, the evaluation of hemorheological factors including platelet counts before PRP can be considered useful in predicting the prognosis of DR.