Iris Neovascularization Research Articles

Cataract in retinopathy of prematurity - A review.

Preterm babies with retinopathy of prematurity (ROP) can become blind if they do not receive appropriate timely intervention. The presence of cataract in these individuals in addition to visual deprivation amblyopia, also delays proper screening, adequate treatment, and makes follow-up assessment difficult. Anatomical differences in these infants and amblyopia management, especially in unilateral cataract, are other important concerns, and hence, management of these cases with cataract and ROP is challenging. In this review, studies where ROP cases were associated with cataract, were evaluated with a focus on preterm individuals less than 6 months age. Preterm babies are at increased risk of developing cataract because of systemic factors. In addition, those with ROP may have cataract associated with retinal detachment or treatment received. The type of cataract, risk factors, and pathophysiology associated with each cause varies. This review highlights these different aspects of cataract in ROP including causes, pathophysiology, types of cataracts, and management. The management of these cases is critical in terms of the timing of cataract surgery and the challenges associated with surgery and posterior segment management for ROP. Anatomical differences, preoperative retina status, pupillary dilatation, neovascularization of iris in aggressive posterior ROP, fundus examination, amblyopia, and follow-up are various important aspects in the management of the same. The preoperative workup, intraoperative challenges, postoperative care, and rehabilitation in these individuals are discussed.

Pattern and risk factors of retinopathy of prematurity in tertiary care centre

Retinopathy of prematurity is one of the commonest cause of blindness in sick neonates exposed to excessive oxygen following NICU admissions. The present study was thus conducted to assess the pattern and risk factors associated with incidence of retinopathy of prematurity.A retrospective record based study was conducted at tertiary care centre between 1st July 2017 to 30thMay 2020 were screened for ROP. Baseline characteristics and risk factors for ROP were assessed. The zone and stage of ROP were categorized as per the International classification of ROP along with iris neovascularisation and plus disease as per the revised international classification of retinopathy of prematurity (ICROP) preplus disease criteria. Data was entered in excel sheet and analysed using SPSS software version 20.Majority of neonates belonged to gestational age of 28 to 31 weeks (58.8%) and 51.2% neonates had birthweight of 1.5 to 2 kg. Male preponderance was observed with male: female ratio of 1.75:1. Amongst the various risk factors, the occurrence of ROP was highly significantly associated with gestational age and birthweight (p<0.01). Subgroup analysis revealed that aggressive posterior ROP (APROP) contributed significantly to Type I ROP in 11.1% (3) cases. And the observed difference in gestational age and birthweight between APROP and other cases of ROP were statistically highly significant (p<0.01).Early and timely screening of ROP for all high risk neonates especially low birth weight and neonates with small gestational age should be mandatory as these are the most significant risk factors associated with ROP in present study.

The Optimization of an Anti-VEGF Therapeutic Regimen for Neovascular Glaucoma

This study investigates the safety and efficacy of conbercept injection through different routes for neovascular glaucoma (NVG) treatment, in which seventy-four patients (81 eyes) with NVG caused by ischemia retinopathy had participated. Patients were divided into three stages according to the progression of NVG and were randomly assigned to receive intracameral or intravitreal conbercept injection. After conbercept injection, patients experienced improved best-corrected visual acuity (BCVA), good intraocular pressure (IOP) control, and neovascularization of Iris (NVI) regression. In stage III, patients required trabeculectomy with mitomycin C plus pan-retinal photocoagulation (PRP) to achieve complete NVI regression. Compared to the intravitreal group, the intracameral group had significantly lower IOP in 2 days in stage III and 1 day in stages I and II after injection, complete NVI regression before PRP in stages I and II, and better NVI regression in stage III. The rates of hyphema after trabeculectomy and malfunction filtering bleb suffering needle bleb revision were lower in the intracameral group, but only the hyphema rate was significantly different. Injections through different routes are all safe. We recommend intravitreal injections for patients in stages I and II, but for stage III, intracameral injection is better, and trabeculectomy with mitomycin C should be conducted within 2 days after injection to maximally reduce the risk of perioperative hyphema.Trial Registration: ClinicalTrials.gov, identifier NCT03154892.

Evolution of practice and management of neovascular glaucoma: a landmark review

AbstractPurposeA comprehensive systematic review (SR) was completed evaluating patient outcomes following medical and surgical interventions targeted at controlling iris neovascularization (NVI) and neovascular glaucoma (NVG).MethodsData sources used were MEDLINE, EMBASE and Web of Science. Studies included both surgical and medical treatments in patients with NVI and NVG. Outcomes measured were intraocular pressure (IOP) lowering, failure rates, loss of visual acuity and disease regression. The SR was registered with PROSPERO.ResultsThe majority of studies retrieved during this time period were population based. A total of 159 studies were included with 148 studies being population based. 59.5% of studies were retrospective in nature and 40.5% were prospective. There were 7 randomised controlled trials and 4 non‐randomised controlled trials. The mean number of patients and eyes studied were 39 ± 42 (range 3–386) and 40 ± 47 (3–428) respectively. The mean follow‐up for all studies was 18.2 ± 24.1 (range 0.25–216) months. Significant differences were observed between glaucoma drainage devices (GDDs), diode laser and trabeculectomy in IOP lowering efficacy and failure rates; particularly with the advent of Anti‐VEGFs.ConclusionsThe unpredictable, uncommon nature of NVG is a significant limitation to high‐quality evidence on the subject. Our findings are primarily based on real‐life, non‐RCT data. We present a necessary update on the medical and surgical treatment of neovascular glaucoma particularly with increased incidence in the era of COVID‐19.

Anti-VEGF Therapy in Ophthalmology

Angiogenesis is when the growth of new blood vessels occurs from the pre-existing vasculature, occurring in both healthy and pathological conditions.Usually, there is a balance maintained between angiogenesis regulators (angiogenesis promoting factors and angiogenesis inhibiting factors), but when this balance is lost, there is either too much or too little angiogenesis. VEGF (Vascular endothelial growth factor) and its receptor (VEGFR) are critical regulators of angiogenesis that promote it.It has been seen that it plays a significant role in the regeneration mechanism of blood vessels, inflammation of body tissues, cancer states, and wound healing. Various pathological conditions show increased VEGF activity.Nowadays, there has been increased use of anti-VEGF drugs, which target the vascular endothelial growth factor and slow down its action. The application of this therapy in ophthalmology is also becoming wider and wider. The implications of anti-VEGF dungs are cancers, rheumatological disorders, macular edema, various retinopathies, glaucoma, etc. 
 Anti-VEGF treatment comprises of three main drugs, namely-Avastin, Lucentis, and Eylea. Their efficiency has been proven to be equal with varying manufacturing costs, packaging, and associated risks.These are the brand names for bevacizumab, ranibizumab, aflibercept, respectively, which have helped us achieve different milestones in treating all kinds of retinal diseases. Several other diseases like iris neovascularization, age-related macular degeneration (AMD), corneal diseases also have been treated using anti-VEGF drugs. Like all drugs, anti-VEGF drugs also have some limitations and side effects, including short half-life, systemic side effects; therefore, the development of new drugs still goes on.

Treatment of Uveal Melanoma With Radioactive Iodine 125 Implant Compared With Proton Beam Radiotherapy.

ObjectiveTo review the current state of radiation therapy for uveal melanoma and compare particle radiation and brachytherapy.Patients and MethodsThe medical records of 156 patients treated for uveal melanoma between May 30, 2012, and March 16, 2020, were retrospectively reviewed. Treatments consisted of either radioactive iodine 125 implant (RAI) or fractionated proton radiation (proton beam therapy [PBT]). Baseline characteristics were compared using a Wilcoxon rank sum test or χ2 test. Outcomes were compared using Cox proportional hazards regression models or logistic regression models.ResultsThe median length of follow-up after treatment was 2.7 years (range, 0.5 to 9.0 years). Patients who underwent treatment with RAI were older (median age, 67 vs 59 years; P<.001) and had a lower tumor classification (American Joint Commission on Cancer; P=.001) compared with those who underwent PBT. There was no significant difference between RAI and PBT in the outcomes of liver metastases, death, enucleation, tearing, vision loss, retinal detachment, tumor thickness, conjunctivitis, optic neuropathy, iris neovascularization, or neovascular glaucoma (all P>.05). Patients who underwent RAI treatment had significantly higher risk of diplopia (P<.001), cataract progression (P<.001), and maculopathy (P=.03) compared with those who received PBT. Patients who underwent RAI were at higher risk of eyelash loss (P=.006) compared with the PBT group.ConclusionTreatment with PBT and RAI has similar efficacy; however, there are differences in the adverse outcomes associated with these 2 modalities.

Choroidal hemangioma in Sturge Weber syndrome: Case series with confirmed tissue diagnosis.

IntroductionSturge-weber syndrome (SWS) is a rare condition that presents with a typical facial port-wine stain, neurological manifestations such as seizures, and ocular involvement by glaucoma and/or choroidal hemangioma. In this series we demonstrate the histopathological details of the primary ocular involvement as well as the late blinding secondary ocular changes.Presentation of casesSeven cases were included with the diagnosis of choroidal hemangioma in association with SWS (6 enucleations and one evisceration). Male to female ratio was 4:3. Age at enucleation/evisceration ranged from 25 to 68 years with a median of 42 years. Five cases had history of glaucoma (71.4%). Diffuse hemangioma was found in all (4 cavernous and 3 mixed cavernous/capillary type). Conjunctival and episcleral hemangiomas were found in 3/7. Iris neovascularization and retinal detachment were confirmed in 5/7 cases each (71%).DiscussionOur demographic and histopathological findings parallel what was previously concluded in the literature about the lack of gender predilection in SWS, and the most common ocular presentations of glaucoma and choroidal hemangioma, which is mostly diffuse in nature. The hemangioma type was found to be mostly cavernous followed by mixed capillary and cavernous. We demonstrated late associated ocular changes such as cataract, iris neovascularization, exudative retinal detachment, retinal pigment epithelium hyperplasia/metaplasia, and optic nerve atrophy, all of which aid in the poor visual outcome in these patients.ConclusionSturge-weber syndrome is a rare but visually disabling disease due to the associated ocular manifestations of glaucoma and choroidal hemangioma. Multidisciplinary approach because of the diverse presentation of this condition by pediatrician, neurologist, and ophthalmologist is essential with an attempt to preserve vision.

Ocular signs of carotid stenosis in ipsi- and contralateral eyes before and after carotid endarterectomy: a prospective study.

We describe hypoperfusion-related and embolic ocular signs of carotid stenosis (CS) before and six months after carotid endarterectomy (CEA) in a CS population. We enrolled prospectively 70 CEA patients (81% male, mean age 69) and 41 non-medicated control subjects (76%, 68), from March 2015 to December 2018, assessing intraocular pressure (IOP), best-corrected visual acuity (BCVA) in logMAR units and performing a bio-microscopy examination. Main index symptoms included amaurosis fugax (Afx) (29, 41%) and hemispheric TIA (17, 24%), and 17 (24%) were asymptomatic. Of the 70, 17 patients (24%, 95% CI 16-36) showed ocular signs of CS. Of four embolic (Hollenhorst plaques) findings, one small macular plaque disappeared postoperatively. Four had hypoperfusion, that is ocular ischaemic syndrome (OIS), requiring panretinal photocoagulation: one for multiple mid-peripheral haemorrhages, two for iris neovascularization and one for neovascular glaucoma (NVG); only the NVG proved irreversible. Nine (de novo in three) showed mild OIS, that is only few mid-peripheral haemorrhages, ranging pre- /postoperatively in ipsilateral eyes from one to eleven (median two)/ one to two (median one), and in contralateral eyes from three to nine (median five)/ one to six (median three). Pre- and postoperative median BCVA was 0 or better, and mean IOP was normal, except in the NVG patient. Temporary visual impairment from 0 to 0.3 occurred in one eye soon after CEA due to ocular hyperperfusion causing macular oedema. Ocular signs of CS are common in CEA patients, ranging from few mid-peripheral haemorrhages to irreversible NVG. Clinicians should be aware of these signs in detecting CS.

Combined intravitreal ranibizumab and zone I sparing laser ablation in infants with posterior zone I retinopathy of prematurity.

Purpose:To evaluate the efficacy of combined intravitreal ranibizumab (IVR) and zone I sparing laser ablation in infants with posterior zone I Retinopathy of Prematurity (ROP).Methods:This was a retrospective, interventional case series including premature infants diagnosed with posterior zone I ROP (n = 24) on ROP screening. Charts and RetCam images of preterm infants with posterior zone I ROP treated with immediate IVR and zone I sparing laser ablation at 4 weeks between April 2016 and September 2019 were reviewed. Data were analyzed and tabulated using frequency and descriptive statistics to describe the demography, morphology, and treatment outcomes. Primary outcome measure was structural outcome at 6 months. It was further categorized as favorable and unfavorable.Results:Twenty-four infants (48 eyes) with a mean gestational age of 28.54 ± 1.98 weeks and birth weight of 1180.33 ± 280.65 grams were analyzed. Thirty-six (75%) eyes had persistent tunica vasculosa lentis and twenty-six (54.1%) eyes had iris neovascularization. All eyes had features of aggressive posterior retinopathy of prematurity (APROP) limited to posterior zone I. The mean duration between IVR and zone I sparing laser ablation was 29.62 ± 6.36 (range: 24-34) days. One infant (2 eyes) received a second IVR treatment for recurrence of plus disease and persistent new vessels close to the fovea. Laser augmentation was done in 13 (27.1%) eyes. A favorable structural outcome was seen in 45 (93.7%) eyes.Conclusion:Posterior zone I ROP presents as APROP. Combined IVR and zone I sparing laser ablation appears effective treatment option in these eyes.

Neovascular Glaucoma after Diabetic Vitrectomy: Incidence and Risk Factors

Purpose: The prevalence and risk factors of neovascular glaucoma (NVG) after diabetic vitrectomy were evaluated. Methods: This retrospective study included 171 eyes of 141 patients who underwent diabetic vitrectomy in-hospital between March 2013 and July 2019 and were followed for &gt;12 months postoperatively. Regardless of the presence or absence of neovascularization in the anterior segment, all patients received injections of intravitreal bevacizumab during vitrectomy. Patients with preoperative neovascularization in iris (NVI) or angle (NVA) received both intracameral and intravitreal bevacizumab injections. Data were collected regarding baseline demographics, preoperative best-corrected visual acuity, intraocular pressure, hypertension, NVG in the fellow eye, panretinal photocoagulation history, iris and angle neovascularization, and postoperative findings (e.g., rebleeding and residual retinal detachment). Results: In total, 141 patients and 171 eyes were included in the study, and the incidence of postoperative NVG was 5.85% (10 patients). Five patients (27.78%) with preoperative NVI or NVA developed postoperative NVG. Significant risk factors for postoperative NVG were preoperative NVA or NVI (odds ratio [OR] = 16.428, p = 0.003), shorter diabetic duration (OR = 0.853, p = 0.033), and the absence of preoperative panretinal photocoagulation (OR = 0.006, p = 0.035). Conclusions: There is a high possibility of postoperative NVG in patients with preoperative NVI or NVA, a short duration of diabetes, and no preoperative panretinal photocoagulation. In such patients, close monitoring is required after diabetic vitrectomy.

Комбинированное лечение тяжелых форм диабетической ретинопатии

Purpose. To evaluate the efficacy and safety of combined treatment of proliferative diabetic retinopathy (PDR), including primary vitrectomy and delayed single-stage patterned panretinal retinal laser coagulation (PLC). Material and methods. The study included 28 patients (28 eyes) with newly diagnosed PDD complicated by hemophthalmos and / or local traction retinal detachment with or without 1-2 stage gliosis, against the background of sub- or decompensation of the course of diabetes mellitus (DM). At the initial examination, a standard ophthalmological examination was performed, as well as fundus photography (Visucam 500, Carl Zeiss, Germany), optical coherence tomography (OCT) (STRATUS OCT Carl Zeiss, Germany). The best corrected visual acuity (BCVA) at admission ranged from light projection to 0.4. All patients were undergone combined treatment. Results. 1-1.5 months after pattern PLC, patients showed regression of neovascularization, ischemic zones were completely blocked, in cases of iris neovascularization, its regression was noted. According to OCT data, the height of edema in the macular zone did not increase. In all cases, the removal of silicone oil was completed within 1-2 months. The indices of BCVA increased and varied from 0.1 to 0.7 after the removal of the silicone oil. According to OCT data, 17 patients showed a decrease in the height of retinal edema in the macular zone from 73 to 150 µm. Conclusion. In the postoperative period after vitreoretinated surgery in patients with PDR, one-stage patterned PLC allows to stabilize the course of the disease in a shorter time and shorten the time of silicone tamponade of the vitreous cavity. Key words: proliferative diabetic retinopathy, vitrectomy, silicone tamponade of the vitreous cavity, patterned panretinal laser coagulation of the retina.

Primary Tumour Type, Clinical Features, Treatment and Outcome of Patients with Iris Metastasis

ABSTRACT Purpose To describe the primary tumour type, clinical features, treatment and outcome of patients with Iris metastasis. Methods Retrospectively analyzed articles published from 1934 to 2019 in the PubMed database. Results In total, 133 eyes of 125 patients with iris metastatic carcinoma were retrieved. The average age at metastasis diagnosis of the patients was 56 ± 15 years; 60 left eyes and 49 right eyes were involved. The most common primary tumors were lung carcinoma (42%) and breast carcinoma (15%). Approximately one-third of the patients were first diagnosed in the ophthalmology department before the primary tumor was detected. Twenty-two percent of iris metastases were discovered before and 33% were discovered after systemic metastasis. The most common complaints were blurred vision and pain. The clinical features included iris masses, neovascularization and keratic precipitates. 57 patients (64%, N = 90) had an elevated intraocular pressure. Local administration of radiation therapy or intraocular injections of anti-VEGF drugs relieved eye discomfort and controlled the high intraocular pressures. Conclusions Iris nodules with increased intraocular pressure and neovascularization may indicate iris metastasis. Lung cancer is the most common primary tumor.

Role of bevacizumab intraocular injection in the management of neovascular glaucoma.

To assess the long-term effects of intraocular bevacizumab (Avastin) injections as an adjunctive drug to manage patients with neovascular glaucoma (NVG). A retrospective study was conducted consisting of 34 eyes with secondary NVG caused by proliferative diabetic retinopathy (n=25), ischemic central retinal vein occlusion (n=8), and retinal ischemia resulting from persistent detachment (n=1) were managed by intraocular injections of bevacizumab (1.25 mg/0.05 mL), in addition to other treatments. The main outcome measure was the change in the degree of iris neovascularization. Secondary outcomes included intraocular pressure and the number of additional interventions or antiglaucoma medications administered after injection. All patients were followed-up for at least 12mo. At the last follow-up, complete regression of rubeosis irides was detectable in 13 (38.2%) eyes and incomplete regression in 21 eyes (61.8%). The mean intraocular pressure was 45.32±7.185 mm Hg at baseline and significantly decreased to 26.15±5.679 mm Hg at the last follow-up visit (P=0.000005). Patients received an average of 4.97 injections. As additional treatments, 12 eyes (35%) received laser photocoagulation and 6 eyes (18%) underwent retinocryopexy. No further treatment was needed in 16 eyes (47.1%). Intravitreal bevacizumab injection can have a favorable effect in controlling intraocular pressure and pain control in patients with NVG because it decreases the angiogenesis and helps to augment the results of conventional procedures. The primary cause of retinal ischemia should be always targeted.

MR Imaging–Pathologic Correlation of Uveal Melanomas Undergoing Secondary Enucleation after Proton Beam Radiotherapy

Background: Currently, radiotherapy represents the most widely employed therapeutic option in patients with uveal melanoma. Although the effects of proton beam radiotherapy on uveal melanoma end ocular tissues have been histologically documented, their appearance at MR imaging is still poorly understood. The purpose of our study was to elucidate the magnetic resonance (MR) semiotics of radiotherapy-induced changes to neoplastic tissues and ocular structures in patients with uveal melanoma undergoing secondary enucleation after proton beam radiotherapy. Methods: Nine patients with uveal melanoma who had undergone proton beam radiotherapy, MR imaging, and subsequent secondary enucleation were retrospectively selected. The histopathologic findings evaluated for irradiated tumors were necrosis, fibrosis, and viable tumor, while the histopathologic findings evaluated for extratumoral ocular/periocular tissues were radiation-related intraocular inflammation, vitreous hemorrhage, optic nerve degeneration, iris neovascularization, and periocular fibrotic adhesions. On MR images, the appearance of the abovementioned histologic features was assessed on conventional and diffusion-weighted sequences. Results: T2-weighted sequences performed better in detecting radiation-induced necrosis, fibrosis, optic nerve degeneration, and periocular fibrotic adhesions. T1-weighted sequences were preferable for identifying cataracts, vitreous hemorrhage, and inflammatory complications. Contrast-enhanced T1-weighted sequences were irreplaceable in assessing iris neovascularization, and in confirming inflammatory complications. Conclusions: In the light of their increasing role in the multidisciplinary management of patients with uveal melanoma, radiologists should be aware of the MR appearance of the effects of radiotherapy on neoplastic and ocular tissue, in order to improve the accuracy of follow-up MR examinations.

The Clinical Characteristics of Noninfectious Occlusive Retinal Vasculitis

To characterize the clinical features of occlusive retinal vasculitis (ORV). Retrospective case series. Forty-two patients with ORV. A retrospective chart review identified all patients with ORV seen at the University of Colorado uveitis service between January 2013 and April 2020. All included patients demonstrated noninfectious uveitis and evidence of vascular occlusion in the presence of retinal vascular inflammation on widefield fluorescein angiography. Demographic data, visual acuity, clinical findings, and fluorescein angiography findings. We identified 73 eyes from 42 patients (15 men, 27 women) with ORV. Thirty-one of 42 patients had bilateral disease. Most eyes (54/73) showed mixed arteriolar and venous vasculitis compared with primarily arteriolar (6/73) or venous (15/73) vasculitis. Thirteen of 42 patients had an underlying systemic condition, most commonly granulomatosis with polyangiitis; however, bilaterality was not associated with a systemic condition. Retinal nonperfusion was present equally in zone 2 (28/73) and zone 3 (28/73) compared with zone 1 (16/73). Retinal or iris neovascularization was present in 25 of 73 eyes. Eighteen of 42 patients required more than 1 immunosuppressive medication (average, 1.33) to prevent progressive vascular occlusive disease. Occlusive retinal vasculitis is a heterogeneous entity with significant risk of visual impairment. Systemic disease was more prevalent in this specific cohort compared with cohorts from prior studies of retinal vasculitis.

Iris Infiltration as a Sign of Relapse in a Child with Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is an uncommon disease of childhood, and anterior segment findings are even rarer. A 3-year-old patient with a history of CML in remission presented after 2 weeks of left eye redness. Examination revealed both a hypopyon and iris infiltration, which were the initial signs of relapse of his leukemia. RETCAM anterior-segment images of the normal right eye (Fig A) and affected left eye (Fig B) are shown. Note the heterochromia, 360 degrees of iris neovascularization, thickening, loss of crypts, and temporal shallow chamber of the left eye, showing infiltration of the iris (Magnified version of Fig A-B is available online at www.aaojournal.org).

Intracameral anti-VEGF injection for advanced neovascular glaucoma after vitrectomy with silicone oil tamponade.

To evaluate the effect of intracameral injection of conbercept for the treatment of advanced neovascular glaucoma (NVG) after vitrectomy with silicone oil tamponade. Conbercept 0.5 mg/0.05 mL was injected into the anterior chamber of 5 eyes, which had developed advanced NVG after vitrectomy with silicone oil tamponade. Then, trabeculectomy with mitomycin C and pan-retinal photocoagulation (PRP) or extra-PRP were conducted within 2d. The follow-up time was 6mo. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), neovascularization of iris (NVI) were recorded before and after treatment. Within 2d after injection, IOP control, and NVI regression were optimal for trabeculectomy. Hyphema occurred in one eye in the process of injection. But none of them present hyphema after trabeculectomy. At the end of follow-up time, all eyes had improved BCVA, well-controlled IOP, and completely regressed NVI. Intracameral injection of conbercept is safe and effective in the treatment of patients with advanced NVG after vitrectomy with silicone oil tamponade. Within 2d after injection is the optimal time window for trabeculectomy, which can maximally reduce the risk of perioperative hyphema.

This issue of Acta Feb 2021

This issue of Acta Feb 2021

Clinical characteristics and germline mutation spectrum of RB1 in Chinese patients with retinoblastoma: A dual-center study of 145 patients

Retinoblastoma (Rb) is the most common primary intraocular childhood malignancy and one of the main causes of blindness in children. In China, most tumors are diagnosed at an advanced stage and have relatively poor outcomes compared to developed countries. Here, we aimed to update the clinical manifestations and RB transcriptional corepressor 1 (RB1) mutation spectrum in Chinese Rb patients. Medical charts of 184 eyes in 145 Chinese Rb patients belonging to unrelated families were reviewed. Genomic DNA was isolated from peripheral blood of the patients and their parents. Mutation analysis of whole coding regions, promoter regions and flanking splice sites in the RB1 gene was performed. In addition, multiplex ligation-dependent probe amplification (MLPA) was done to detect gross aberrations. Germline RB1 mutations were observed in 37.2% (54/145) of Rb patients. RB1-mutated patients presented with earlier age of diagnosis (p = 0.019), with a significantly larger proportion of bilateral cases (p = <0.001) and secondary malignancies (p = 0.027) relative to those without RB1 mutations. For ocular clinical presentations, RB1-mutated retinoblastomas presented with a larger proportion of ectropion uveae (p = 0.017) and iris neovascularization (p = 0.001). These RB1 mutations comprised of 13 (24.1%) nonsense mutation, 13 (24.1%) splicing mutations, 11 (20.4%) frameshift deletions, 11 (20.4%) gross mutations, 3 (5.6%) missense mutations, 2 (3.7%) promoter mutations and 1 (1.9%) non-frameshift deletion. In addition, 8 novel RB1 mutations were identified. These germline RB1 mutations were not related to age at diagnosis or laterality. Here, we provide a comprehensive spectrum of RB1 germline mutations in Chinese Rb patients and describe correlations between RB1 mutations and clinical presentations. Our study also provides new evidence that will inform management and genetic counselling of Rb patients and families.

Ocular complications following intravitreal bevacizumab injection for retinopathy of prematurity and assessment of risk factors

PurposeLaser ablation of the avascular peripheral retina has been the standard method of ROP treatment. Intravitreal anti-VEGF is useful in the management of ROP patients, especially for aggressive posterior ROP. However, ocular and systemic complication after intravitreal bevacizumab was the main concern. This study aimed to investigate the treatment-related ocular and systemic complications of intravitreal bevacizumab (IVB) in patients with retinopathy of prematurity (ROP).MethodThis retrospective study included neonates receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) to treat ROP. Medical records of the patients were evaluated about the ocular complications after receiving IVB from 2012 to 2019. Treatment-related complications (vitreous hemorrhage, glaucoma, cataract, hyphema, corneal abrasion/opacity, and endophthalmitis), and disease-progression signs including retinal fold or stage 4 or 5 detachment were documented. Any reports of systemic events after injections were also recorded.ResultMean gestational age and birth weight of 441 patients receiving IVB for type-1 ROP were 28 ± 2 (22–34 weeks) and 1121 ± 312 (550–2700 g), respectively. The median follow-up after treatment in all patients and patients with complications was 289.43 ± 257 days (5–1899 days) and 385.89 ± 311.59 (196–1192) days, respectively. Out of 865 eyes, 20 eyes (2.31%, 95% Clopper-Pearson Confidence Interval: 1.14–3.54%) have been affected by ocular complications. The rates of different complications included progression of retinopathy in 17 eyes (1.96%), cataracts in 2 eyes (0.23%), and vitreous hemorrhage in one eye (0.11%). No cases of endophthalmitis, thromboembolic events, or death occurred in this study. We evaluated the prevalence ratio (PR) on the multiple risk factors to determine the prediction of the complications. The existence of neovascularization of iris has the highest susceptibility to predict the complication (PR = 5.091, P-value 0.014) following by the presence of retinopathy in zone 1 of the infant’s retina (PR = 4.386, P-value = 0.010).ConclusionThe incidence rate of complications related to Intravitreal bevacizumab injection was low, which was compatible with previous studies. Bevacizumab injection seems well tolerated in most cases of ROP. Iris neovascularization and the presence of retinopathy in zone 1 were associated with a higher occurrence of complications than the absence of these risk factors.