Primary congenital glaucoma surgery: outcomes and visual function.

PURPOSE: To assess the long-term visual outcomes of children with PCG, irrespective of the type of surgical procedure, and to create visual acuity curves to help in predicting the development of visual function in these patients. The secondary aim is to identify associated factors for visual decline or loss, highlighting differences between neonatal and infantile subgroups. METHODS: The medical records of pediatric glaucoma patients from 1996 to 2017 at the University Hospital of Verona (Verona, Italy) were retrospectively reviewed. Visual acuities, surgeries, PCG subtype and etiology of vision impairment were recorded. Statistical analyses were performed to detect factors associated with vision decline. RESULTS: Sixty-seven eyes (40 patients) were included in the study. Developmental predictive curves of visual acuity showed that children with infantile PCG had a better visual outcome than children with neonatal PCG at each step of follow-up. A good-to-moderate VA (< 1 LogMAR) was achieved in 56 eyes (83.6%), while 11 eyes (16.4%) had poor VA (≥ 1 LogMAR). The age at onset, sex, number of surgeries, intraocular pressure (IOP) control (with or without antiglaucoma drugs), axial length (AL) and corneal opacities were statistically associated with vision impairment (p < 0.01). The main cause of visual impairment was amblyopia. CONCLUSIONS: Visual outcomes of PCG significantly correlate with the age at diagnosis. Although a good long-term IOP control can often be achieved in PCG, often the visual acuity remains below the lower limits of the normal range. Poor vision in childhood is related to global developmental problems, and referral to third-level services should not be delayed to prevent vision impairment. In this regard, visual acuity curves can be a useful tool for the consultant ophthalmologist to define the visual development of children affected by PCG.

The effect of pars plana vitrectomy with internal limiting membrane peeling on the durability of the intravitreal dexamethasone implant in the treatment of diabetic macular edema.

PURPOSE: To evaluate the influence of pars plana vitrectomy with internal limiting membrane peeling on recurrence time of diabetic macular edema in eyes under treatment with dexamethasone intravitreal implant injections. MATERIAL AND METHODS: Twelve pseudophakic eyes of 12 patients with non-proliferative diabetic retinopathy and non-tractional diabetic macular edema were included. All eyes had already been treated with two or more dexamethasone intravitreal implant injections evidencing a recurrence time of three months or less (early recurrence). At baseline, they underwent pars plana vitrectomy with internal limiting membrane peeling, ending with dexamethasone intravitreal implant injection. Patients were then followed-up monthly, treated with a second injection at the first recurrence, and followed up to the second recurrence. Measurements of best corrected visual acuity, intraocular pressure, and central foveal thickness by spectral-domain optical coherence tomography were performed at each follow-up examination. RESULTS: Vitrectomized eyes showed a significant extension of recurrence time of diabetic macular edema, and specifically from 3.4 (3.2-3.7) to 6.5 (5.7-8.2) months after the first injection, and to 7.0 (5.7-8.2) months (p < 0.01) after the second injection (p < 0.01). CONCLUSIONS AND IMPORTANCE: Pars plana vitrectomy with internal limiting membrane peeling seems not to influence functional and anatomical results in eyes under treatment with dexamethasone intravitreal implant injections for diabetic macular edema, but appears to significantly extend the benefit of the drug.

Early and late onset sepsis and retinopathy of prematurity in a cohort of preterm infants.

This study investigates the impact of antenatal and postnatal infection or inflammation on the onset and progression of Retinopathy of Prematurity (ROP). We retrospectively collected clinical and demographic data of preterm infants with birth weight ≤ 1500 g or gestational age < 30 weeks admitted to the neonatal intensive care unit of Verona from 2015 to 2019. Uni- and multivariable analysis was performed to evaluate the potential effect of selected variables on the occurrence of any stage ROP and its progression to severe ROP, defined as ROP requiring treatment. Two hundred and eighty neonates were enrolled and 60 of them developed ROP (21.4%). Oxygen need for 28 days and late-onset sepsis (LOS) increased the risk of any grade ROP after adjusting for birth weight and gestational age (OR 6.35, 95% CI 2.14-18.85 and OR 2.49, 95% CI 1.04-5.94, respectively). Days of mechanical ventilation and of non-invasive ventilation increased the risk of progression to severe ROP after adjusting for birth weight and gestational age (OR 1.08, CI 1.02-1.14 and OR 1.06, CI 1.01-1.11, respectively). Exposure to infection with production of inflammatory mediators may contribute to increase the risk of ROP occurrence in very preterm neonates.

Early DMO: a predictor of poor outcomes following cataract surgery in diabetic patients. The DICAT-II study.

BACKGROUND: The prospective DIabetes and CATaract Study II (DICAT II) was performed to characterise the risks of cataract surgery to the retinae of patients with early diabetic macular oedema (E-DMO). METHODS: DICAT II was a prospective, comparative, multicentre, observational study involving six Italian clinics. Patients were aged ≥55 years, had type 1 or 2 diabetes with spectral-domain optical coherence tomography evidence of ESASO classification Early DMO. Group 1 eyes (78 eyes, 78 patients) underwent phacoemulsification-based cataract surgery. Group 2 eyes (65 eyes, 65 patients) had E-DMO and either clear media or had undergone uncomplicated cataract surgery ≥1 year previously. Central subfield thickness (CST) and best-corrected visual acuity (BCVA) were assessed in both groups. RESULTS: The negative impact of surgery on CST was evident after the first postoperative week; CST peaked during the first month, then rapidly decreased. CST worsening ≥10 µm was observed in 63/78 eyes (80.7%) and 29/65 eyes (44.6%) in Groups 1 and 2, respectively (p < 0.0001). CST worsening of ≥50 µm was observed in 51 eyes (65.4%) and 10 eyes (15.4%) in Groups 1 and 2, respectively (p < 0.0001). Mean CST worsening was lower in Group 2 than in Group 1 (38.6 ± 30.4 µm vs 85.5 ± 55.3 µm, p < 0.0001) with a lower BCVA loss (-2.6 ± 3.5 letters vs -8.2 ± 6.2 letters, p < 0.0001). Higher glycaemic levels and HBA1c levels were significantly associated with the risk of >50 µm CST worsening in eyes from both groups. CONCLUSION: Early DMO is associated with poorer outcomes after cataract surgery and requires close pre- and postoperative monitoring.

Surgical Antimicrobial Prophylaxis in Patients of Neonatal and Pediatric Age Subjected to Eye Surgery: A RAND/UCLA Appropriateness Method Consensus Study.

Ocular surgery encompasses a wide range of procedures, including surgery of the tear ducts, eyelid, cornea and conjunctiva, lens, ocular muscle, and vitreoretinal and iris surgery. Operations are also performed for the removal of tumors, repairs of ocular trauma and, finally, corneal transplantation. Antibiotic prophylaxis for the prevention of surgical site infections (SSIs) in ocular surgery is a complex field in which shared lines of action are absent. In light of the scarcity of shared evidence in the use of ocular antimicrobial prophylaxis for the pediatric population, this consensus document aims to provide clinicians with a series of recommendations on antimicrobial prophylaxis for patients of neonatal and pediatric age undergoing eye surgery. The following scenarios are considered: (1) intraocular surgery; (2) extraocular surgery; (3) ocular trauma; (4) ocular neoplasm; (5) ocular surface transplantations; (6) corneal grafts. This work has been made possible by the multidisciplinary contribution of experts belonging to the most important Italian scientific societies and represents, in our opinion, the most complete and up-to-date collection of recommendations regarding clinical actions in the peri-operative environment in eye surgery. The application of uniform and shared protocols aims to improve surgical practice, through the standardization of procedures, with a consequent reduction of SSIs, also limiting the phenomenon of antimicrobial resistance.

Pediatric eye emergency department activity during the first wave of Covid-19 pandemic.

BACKGROUND: We investigated the volume and the characteristics of pediatric eye emergency department (PEED) consultations performed at our tertiary eye center during the early months of the COVID-19 pandemic and we compared them to those carried out in the same time interval of the previous three years. METHODS: Ophthalmic emergency examinations of patients aged ≤18 years old and done during the national COVID-19 lockdown (March 9th, 2020 - May 3rd, 2020) and in the corresponding date range of the previous three years (2017, 2018, and 2019) have been considered and reviewed. The following features were retrieved and analyzed: age, gender, duration and type of accused symptoms, traumatic etiology, and the discharge diagnosis. RESULTS: 136, 133, and 154 PEED visits have been performed respectively in 2017, 2018, and 2019, while 29 patients presented in 2020. Therefore, the volume of PEED activity decreased by 79.4% (p < 0.0001). Demographical and clinical characteristics were comparable to those of the pre-COVID period. Despite the absolute reduction in the number of traumas, urgent conditions increased significantly from 30.7 to 50.7% (p = 0.024). CONCLUSIONS: PEED activity decreased consistently after the onset of the pandemic and it was mainly attended by those children whose conditions required prompt assistance, reducing the number of patients diagnosed with milder pathologies. At the end of the emergency, better use of PEED could avoid overcrowding and minimize waste, allowing resource optimization for the management of urgent cases.

Flavonoid supplements increase neurotrophin activity to modulate inflammation in retinal genetic diseases.

Retinal degenerative disorders induce loss of photoreceptors associated with inflammation, and negative remodeling and plasticity of neural retina. Retinal degenerative diseases may have genetic and/or environmental causes. Degeneration of retinal pigment epithelium cells initiates a vicious circle increasing the ongoing inflammation in both retina and choroid. Flavonoids are polyphenolic molecules with antioxidant activity and  dietary intake, specifically of anthocyanins and flavanols, improves oxidative stress and neuro-inflammation. In vitro and ex vivo studies have also revealed biological effects of flavonoids on retinal protection against oxidative stress and inflammation. In this brief review, the protective role of flavonoids against retinal degeneration and inflammation will be discussed along with their therapeutic potential for the treatment of retinal degenerative diseases.

CRB1-Related Cystic Maculopathy in Twins Conceived Through Heterologous Fertilization With Variant-Carrying Oocytes.

Cystic maculopathy has been associated with genetic disorders such as retinitis pigmentosa, X-linked retinoschisis, cone dystrophy, and foveal retinoschisis. Familial foveal retinoschisis was recently described as a rare disease caused by CRB1 variants. The authors report the phenotype-genotype pattern of a pair of dizygotic twins with early-onset cystic maculopathy due to CRB1 pathogenic variants. The twins were conceived by heterologous fertilization with variant-carrying oocytes. The probands were monitored for a period of 4 years. Next generation sequencing of a panel of genes responsible for retinal dystrophies was performed. Both children carried three pathogenic variants in CRB1: a novel heterozygous truncating variant p.(Val855*) inherited from the father and two known heterozygous missense variants, p.[(Phe144Val; Thr745Met)], inherited from the oocyte donor. The findings confirm that CRB1 variants can be responsible for foveal retinoschisis with variable clinical expressivity ranging from schitic macular alteration to early-onset forms of cystic maculopathy. The authors highlight the importance of exome analysis of gamete donors to assess the likelihood of recessively inherited disorders by means of a prediction algorithm able to combine parent and donor exome data. [J Pediatr Ophthalmol Strabismus. 2020;57:e19-e24.].

Long-Term Anatomic and Visual Outcome Following Vitrectomy for Stage 4B and 5 Retinopathy of Prematurity.

BACKGROUND AND OBJECTIVES: Surgical indications in stages 4B and 5 retinopathy of prematurity (ROP) are not universally accepted. The authors' purpose is to evaluate the long-term anatomic and visual outcomes of vitrectomy for retinal detachment (RD) associated with stages 4B and 5 ROP. PATIENTS AND METHODS: Data of patients who consecutively underwent vitrectomy for stages 4B and 5 ROP from 1999 to 2013 were retrospectively reviewed and included grade of retinal attachment and visual acuity (VA) at the last follow-up. RESULTS: Seventy eyes of 38 infants were included: 23 with stage 4B and 47 with stage 5 ROP. Lens-sparing vitrectomy was performed in 11 eyes, combined lensectomy / vitrectomy in 59 eyes. Mean follow-up was 8.5 years. Anatomic success was maintained in 41 eyes (58.5%), and among them, VA greater than 5/200 was achieved in 17 eyes (41.4%). CONCLUSION: The long-term visual and anatomic success rates were encouraging for the surgical correction of RD associated with late stages ROP. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:208-214.].

Morphologic Criteria of Lesion Activity in Neovascular Age-Related Macular Degeneration: A Consensus Article.

Intravitreal antivascular endothelial growth factor drugs represent the current standard of care for neovascular age-related macular degeneration (nAMD). Individualized treatment regimens aim at obtaining the same visual benefits of monthly injections with a reduced number of injections and follow-up visits, and, consequently, of treatment burden. The target of these strategies is to timely recognize lesion recurrence, even before visual deterioration. Early detection of lesion activity is critical to ensure that clinical outcomes are not compromised by inappropriate delays in treatment, but questions remain on how to effectively monitor the choroidal neovascularization (CNV) activity. To assess the persistence/recurrence of lesion activity in patients undergoing treatment for nAMD, an expert panel developed a decision algorithm based on the morphological features of CNV. After evaluating all current retinal imaging techniques, the panel identified optical coherent tomography as the most reliable tool to ascertain lesion activity when funduscopy is not obvious.

Parent-of-origin effect of hypomorphic pathogenic variants and somatic mosaicism impact on phenotypic expression of retinoblastoma.

Retinoblastoma is the most common eye cancer in children. Numerous families have been described displaying reduced penetrance and expressivity. An extensive molecular characterization of seven families led us to characterize the two main mechanisms impacting on phenotypic expression, as follows: (i) mosaicism of amorphic pathogenic variants; and (ii) parent-of-origin-effect of hypomorphic pathogenic variants. Somatic mosaicism for RB1 splicing variants (c.1960+5G>C and c.2106+2T>C), leading to a complete loss of function was demonstrated by high-depth NGS in two families. In both cases, the healthy carrier parent (one with retinoma) showed a variant frequency lower than that expected for a heterozygous individual, indicating a 56-60% mosaicism level. Previous evidences of a ~3-fold excess of RB1 maternal canonical transcript led us to hypothesize that this differential allelic expression could influence phenotypic outcome in families at risk for RB onset. Accordingly, in five families, we identified a higher tumor risk associated with paternally inherited hypomorphic pathogenic variants, namely a deletion resulting in the loss of 37 amino acids at the N-terminus (c.608-16_608del), an exonic substitution with a "leaky" splicing effect (c.1331A>G), a partially deleterious substitution (c.1981C>T) and a truncating C-terminal variant (c.2663+2T>C). The identification of these mechanisms changes the genetic/prenatal counseling and the clinical management of families, indicating a higher recurrence risk when the hypomorphic pathogenic variant is inherited from the father, and suggesting the need for second tumor surveillance in unaffected carriers at risk of developing adult-onset cancer such as osteosarcoma or leiomyosarcoma.

Dexamethasone intravitreal implant at the time of cataract surgery in eyes with diabetic macular edema.

PURPOSE: To determine the potential role of intraoperative dexamethasone intravitreal implant (DEX-I) in reducing diabetic macular edema (DME) worsening after phacoemulsification. METHODS: This was a prospective study on 19 eyes of 19 patients with type 2 diabetes mellitus with DME and cataract. Mean preoperative Early Treatment Diabetic Retinopathy Study visual acuity (VA) was 16.7 letters. Mean foveal thickness (FT) was 451 µm. The DME was naive in 11 eyes and refractory in 8 eyes. All eyes underwent a standard phacoemulsification and intraocular lens implantation; DEX-I was injected at the end of surgery. Follow-up was performed at 1 week and then monthly until DME recurrence (up to 8 months). RESULTS: At 1 week, mean VA improved by 15 letters (range 0-29 letters) and mean FT decreased by 147 µm (range 69-236 µm). Improvement consolidated at month 1, with a mean VA improvement of 18 letters (range 3-32 letters) and a mean improvement in FT of 193 µm (range 76-304 µm), remaining stable at month 2 after surgery in all eyes. The DME recurred in 1 eye at month 3, in 14 eyes (73.8%) between months 4 and 5, and after month 6 in 4 eyes (21%). Refractory DMEs demonstrated the same benefit but recurred earlier than naive ones (4 months versus 5.8 months, p<0.01). CONCLUSIONS: Intraoperative DEX-I prevents DME worsening after phacoemulsification. Its positive effects last for at least 3 months.

Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a complex disorder characterized by incomplete development of the retinal vasculature. Here, we report the results obtained on the spectrum of genetic variations and correlated phenotypes found in a cohort of Italian FEVR patients. Eight probands (age range 7-19 years) were assessed by genetic analysis and comprehensive age-appropriate ophthalmic examination. Genetic testing investigated the genes most widely associated in literature with FEVR: FZD4, LRP5, TSPAN12, and NDP. Clinical and genetic evaluations were extended to relatives of probands positive to genetic testing. Six out of eight probands (75%) showed a genetic variation probably related to the phenotype. We identified four novel genetic variants, one variant already described in association with Norrie disease and one previously described linked to autosomal dominant FEVR. Pedigree analysis of patients led to the classification of four autosomal dominant cases of FEVR (caused by FZD4 and TSPAN12 variants) and two X-linked FEVR probands (NDP variants). None of the patients showed variants in the LRP5 gene. This study represents the largest cohort study in Italian FEVR patients. Our findings are in agreement with the previous literature confirming that FEVR is a clinically and genetically heterogeneous retinal disorder, even when it manifests in the same family.

Corrigendum to "Genotype-Phenotype Characterization of Novel Variants in Six Italian Patients with Familial Exudative Vitreoretinopathy".

[This corrects the article DOI: 10.1155/2017/3080245.].

Osteoporosis-pseudoglioma syndrome: Report of two cases and a manifesting carrier.

BACKGROUND: Osteoporosis-pseudoglioma syndrome is a very rare disease mainly characterized by severe eye abnormalities and osteoporosis but also causing a broader range of clinical features. The syndrome is associated with homozygous or compound heterozygous variations in the LRP5 gene. In this report, we describe two children with a severe early-onset form of familial exudative vitreoretinopathy associated with skeletal abnormalities. MATERIALS AND METHODS: Two probands (4 and 7 years of age respectively) and their parents were assessed by genetic analysis and comprehensive ophthalmic examination. RESULTS: In both probands, the diagnosis of osteoporosis-pseudoglioma syndrome was confirmed by detection of three new pathogenic LRP5 variants: p.(Asp379Asn), found in the homozygous state in one proband, and p.(Asp203Ala) in the compound heterozygous state with p.(Cys612Valfs*25) in the other. The clinical and genetic study was extended to their parents, confirming that heterozygous carriers may also have incomplete clinical manifestation of this syndrome. CONCLUSIONS: To our knowledge, these are the first two cases of the syndrome described in Italy. Genetic testing proved to be fundamental for definition of the syndrome and confirms the importance of early detection of LRP5 variants for management of systemic features of the disease in patients and carrier relatives.

Predictive algorithms for early detection of retinopathy of prematurity.

PURPOSE: To evaluate sensitivity, specificity and the safest cut-offs of three predictive algorithms (WINROP, ROPScore and CHOP ROP) for retinopathy of prematurity (ROP). METHODS: A retrospective study was conducted in three centres from 2012 to 2014; 445 preterms with gestational age (GA) ≤ 30 weeks and/or birthweight (BW) ≤ 1500 g, and additional unstable cases, were included. No-ROP, mild and type 1 ROP were categorized. The algorithms were analysed for infants with all parameters (GA, BW, weight gain, oxygen therapy, blood transfusion) needed for calculation (399 babies). RESULTS: Retinopathy of prematurity (ROP) was identified in both eyes in 116 patients (26.1%), and 44 (9.9%) had type 1 ROP. Gestational age and BW were significantly lower in ROP group compared with no-ROP subjects (GA: 26.7 ± 2.2 and 30.2 ± 1.9, respectively, p < 0.0001; BW: 839.8 ± 287.0 and 1288.1 ± 321.5 g, respectively, p = 0.0016). Customized alarms of ROPScore and CHOP ROP correctly identified all infants having any ROP or type 1 ROP. WINROP missed 19 cases of ROP, including three type 1 ROP. ROPScore and CHOP ROP provided the best performances with an area under the receiver operating characteristic curve for the detection of severe ROP of 0.93 (95% CI, 0.90-0.96, and 95% CI, 0.89-0.96, respectively), and WINROP obtained 0.83 (95% CI, 0.77-0.87). Median time from alarm to treatment was 11.1, 5.1 and 9.1 weeks, for WINROP, ROPScore and CHOP ROP, respectively. CONCLUSION: ROPScore and CHOP ROP showed 100% sensitivity to identify sight-threatening ROP. Predictive algorithms are a reliable tool for early identification of infants requiring referral to an ophthalmologist, for reorganizing resources and reducing stressful procedures to preterm babies.

Dexamethasone intravitreal implant for diabetic macular edema: indications for a PRN regimen of treatment.

PURPOSE: To define the mean time of first recurrence of diabetic macular edema (DME) after a single injection of dexamethasone intravitreal implant (DEX-I), reducing the burden of monthly visits during a PRN regimen of treatment. METHODS: Twenty phakic eyes with DME (12 eyes naïve and 8 eyes with edema persistent after previous treatments) were followed monthly after DEX-I injection until evidence of first recurrence of edema, defined as a change in visual acuity (VA) ≥5 letters and/or in foveal thickness (FT) ≥50 µm. Reaching this point, the eyes were re-treated. Monitored parameters were changes in VA, FT, intraocular pressure (IOP), and lens opacity. RESULTS: Maximal efficacy was registered at month 1, when mean VA improved by 14 letters (19%), FT decreased by 325 µm (43.7%), and in 15 eyes (75%) edema was completely reabsorbed. The mean time of first recurrence was 5.1 months. No statistical difference was found between eyes with naïve or persistent DME. Five eyes needed topical medication for modest temporary IOP increase (21-24 mm Hg) between months 2 and 4. No increase in lens opacities was registered during follow-up. CONCLUSIONS: According to the results of this study, the first signs of DME recurrence after DEX-I injection appear at a mean time of 5 months, suggesting that an appropriate and prudent time schedule for a PRN regimen could be limited to monthly tonometry and a first complete examination not before 4 months.

Role of OCT in the diagnosis and follow up of diabetic macular edema.

The aim is to present, along with a brief literature review, the results of OCT scan in eyes with diabetic macular edema (DME), as well as examples of the utility of OCT for different therapeutic approaches. One-hundred and thirty-six eyes with diabetic retinopathy were analyzed with OCT to explore the different patterns of DME. Some eyes with DME were studied with OCT pre and postoperatively to determine the efficacy of photocoagulation and vitrectomy to restore a normal macular profile. Sixty-eight eyes with a central foveal thickness of 200 mu or more were considered "edematous". Three different patterns of DME were recognized and analyzed: macular thickening, cystoid macular edema and shallow retinal detachment. The change in macular profile and internal retinal structure after laser or surgical treatment are well visible with OCT. OCT contributes in understanding the anatomy of DME and the intraretinal damage and seems to be the technique of choice for the follow-up of macular edema. We think that this tool should always be used in monitoring the effect of therapies in future studies.