A Literary Pediatric Retina Fellowship With Michael T. Trese, MD.

Michael T. Trese, MD (1946-2022), a vitreoretinal surgeon, made significant contributions to the field of retina. Although most known for his work in pediatric retina surgery, he was a pioneer in areas such as medical retina, translational research, and telemedicine. This article reviews his major contributions to spread his knowledge more widely to vitreoretinal trainees and specialists. We discuss six areas where Trese made a lasting impact: lens-sparing vitrectomy, familial exudative vitreoretinopathy, congenital X-linked retinoschisis, autologous plasmin enzyme, regenerative medicine, and telemedicine. [Ophthalmic Surg Lasers Imaging Retina 2023;54:701-712.].

Familial exudative vitreoretinopathy with TGFBR2 mutation without signs of Loeys-Dietz syndrome.

Background: Familial exudative vitreoretinopathy (FEVR) is an inherited retinal disorder with high genetic heterogeneity, and it is characterized by a defect in the development of the retinal vascular system. Loeys-Dietz syndrome (LDS) is an autosomal dominant systemic connective tissue disorder that is caused by mutations in the genes related to transforming growth factor signaling systems including the TGFBR2 gene. Two earlier studies reported that patients with LDS from mutations in the TGFBR2 gene were associated with FEVR-like retinal phenotype. The purpose of this study was to determine the characteristics of a case of FEVR without systemic abnormalities who had a mutation in the TGFBR2 gene.Materials and Methods: The clinical appearances and surgical outcomes were determined from the medical records. Genetic analysis was performed by whole exome sequencing.Results: A 15-year-old boy was diagnosed with FEVR by the appearance of the peripheral retina of both eyes and a retinal detachment in the left eye. Whole exome sequencing revealed a heterozygous deletion mutation in the TGFBR2 gene. A de novo mutation was confirmed by examining the family members. No systemic abnormalities were detected in the patient including those associated with LDS.Conclusions: FEVR can be associated with a TGFBR2 mutation without showing signs of LDS.

PHENOTYPIC HETEROGENEITY IN A FAMILY WITH X-LINKED FAMILIAL EXUDATIVE VITREORETINOPATHY WITH PREVENTION OF VISUAL LOSS IN AN AFFECTED MALE CHILD WITH LASER TREATMENT IN INFANCY.

PURPOSE: To present the scope of prenatal diagnosis and early treatment of patients with clinically heterogeneous phenotypic retinal dysplasia associated with NDP gene variants. METHODS: Retrospective. Review of electronic medical records. RESULTS: Twenty-nine-year-old woman known to carry a NDP gene variant presented to the eye clinic for consultation and risk assessment at her second pregnancy. Her 11-year-old son had bilateral retinal detachment, despite surgical treatment. The family declined prenatal testing. The patient was born full term, was examined, and underwent genetic testing after birth. He was found to have bilateral retinal avascular periphery abnormalities and preretinal hemorrhages on the left eye. The patient received bilateral laser treatment at 2 months of age. He was found to be doing well at 16 months after treatment with adequate visual acuity and flat maculae. The asymptomatic mother and maternal grandfather of the proband were found to have retinal periphery abnormalities with unremarkable posterior pole and excellent visual acuity. CONCLUSION: NDP gene variants associated with X-linked familial exudative vitreoretinopathy phenotype benefit from early treatment. Providers who take care of these patients need to monitor closely the pregnancy and delivery of a male child born to a female carrier to offer appropriate and timely treatment.

Analysis of Predisposing Clinical Features for Worsening Traction After Treatment of Familial Exudative Vitreoretinopathy in Children.

PURPOSE: To determine the incidence of worsening vitreoretinal traction after laser treatment for familial exudative vitreoretinopathy (FEVR) and to determine whether any baseline clinical features are associated with worsening. DESIGN: Retrospective cohort comparison study in a university tertiary referral center. METHODS: All patients 0-21 years of age treated with laser from January 1, 2001, to June 1, 2018, were studied. Worsening traction after treatment was defined as the occurrence within 6 months of worsening or development of tractional retinal detachment, folds, dragging, breaks, rhegmatogenous detachment, or worsening tractional membranes. Comparisons of baseline features between groups with and without worsening were performed to determine features associated with higher risk. RESULTS: A total of 46 eyes from 28 patients met inclusion criteria. Of the 46 eyes, 6 (13%) had worsening after treatment. There were no significant differences in age or other baseline demographics between the cohorts with and those without worsening traction. The presence of proliferative tissue in contact with the lens was found in 2 of 6 patients with worsening compared to 1 of 40 (3%) without worsening (P = .04). Mean follow-up was 57.8 months (range, 6.6-134 months). At the 6-month follow-up, median logMAR visual acuity in the cohorts with and without worsening was 1.7 (Snellen 20/1002; n = 5) and 0.24 (Snellen 20/35; n = 16), respectively. CONCLUSIONS: Laser treatment resulted in worsening traction in a substantial proportion of eyes with FEVR. Children with proliferative tissue in contact with the lens may be at higher risk of worsening after laser. Potential measures to reduce risk will require further study to establish efficacy.

Outcome and risk factors of vitreoretinal surgery in pediatric patients with familial exudative vitreoretinopathy.

PURPOSE: To evaluate the outcome for vitreoretinal surgery in children with familial exudative vitreoretinopathy (FEVR) and to evaluate the risk factors associated with failure. METHODS: This is a retrospective interventional case series of 43 consecutive eyes (34 patients) with vitreoretinal surgery for FEVR. Ocular status prior to intervention and at last follow-up and all surgical steps were recorded. Follow-up time was at least 6 months. Main outcome measure was surgical failure (defined as one of the following: (1) deterioration of visual acuity and stage, (2) persistence or development of total retinal detachment, (3) phthisis). RESULTS: After a mean follow-up of 3.3 ± 3.4 years (median 2.3; 0.5-15.7 years), surgery was successful in 30 eyes (70%) and failed in 13 eyes (30%). Twenty-one eyes (49%) improved, 13 (30%) remained stable, and 9 (21%) deteriorated. Postoperatively, stages and VA improved significantly (p = 0.001; p = 0.04, respectively). Surgical failure was only observed on patients with stages 4 and 5. Mean macular thickness decreased significantly in eyes (stages 2 and 3) with tractional epiretinal membrane. CONCLUSION: Eyes with tractional epiretinal membrane in stages 2 and 3 seem to benefit from vitrectomy and membrane peeling with a positive risk-benefit profile. Advanced stages have a low success rate and limited functional improvement, but in selected cases, surgery seems beneficial.

Novel mutation in CTNNB1 causes familial exudative vitreoretinopathy (FEVR) and microcephaly: case report and review of the literature.

Purpose: Neonatal retinal folds and/or vitreoretinal traction can be signs of isolated ocular or syndromic disorders. Etiologies include retinopathy of prematurity, perinatal infections or inherited vitreoretinal disorders such as familial exudative vitreoretinopathy (FEVR) or Norrie disease. We present the clinical and genetic findings of a two-month-old infant with microcephaly, mild motor developmental delay, and FEVR, who required urgent surgical interventions.Methods: The patient underwent an initial examination under anesthesia (EUA) with fluorescein angiography (FA) and subsequent medical and surgical treatments. Genetic testing was undertaken to identify the etiology.Results: Examination at 2 months of age demonstrated microcephaly with a head circumference smaller than the 1st percentile. Family history was negative for microcephaly or retinal disease. Anterior segment eye exam was normal OU. There were bilateral macular folds involving the fovea and extending from the disc to the temporal periphery. FA demonstrated bilateral incomplete vascularization of the retina most notable nasally. Indirect laser was applied to ischemic retina OU. Scleral buckling procedures were performed OU as well as a vitrectomy in the left eye. Follow-up examinations demonstrated the stable appearance of the folds and attached retinas OU. Genetic testing identified a novel dominant heterozygous c.2046_2047del [p.Phe683Glnfs*9] mutation in CTNNB1, predicted to result in a frameshift causing a truncated protein.Conclusions: CTNNB1 mutations are an uncommon cause of FEVR with microcephaly.

MACULAR HOLE IN A YOUNG PATIENT AFFECTED BY FAMILIAL EXUDATIVE VITREORETINOPATHY.

PURPOSE: To report a case of familial exudative vitreoretinopathy in which genetic testing was used to confirm the diagnosis with a new mutation identified in FZD4 gene. METHODS: A 28-year-old girl was addressed to our clinic for surgical management of a macular hole possibly associated with Coats disease. Multimodal imaging was performed including fundus photography, fundus autofluorescence, optical coherence tomography, fluorescein, and indocyanine green angiography. RESULTS: On examination, visual acuity was light perception secondary to previous retinal detachment and 20/32, respectively, in her right and left eye. Clinical and imaging evaluations showed findings suggestive for familial exudative vitreoretinopathy. Spectral domain optical coherence tomography study of the macula showed a macular pucker with lamellar macular hole and a conservative approach was preferred. After 18 months of observation, the patient underwent surgery secondary to the onset of a full thickness macular hole. After 24 months, the patient's vision was 20/32. Genetic testing was used to confirm the diagnosis demonstrating 2 new mutations in FZD4 gene. CONCLUSION: Our case emphasizes the importance of a prompt recognition of familial exudative vitreoretinopathy disease also using gene testing and a close follow-up to prevent and manage possible complications.

Bilateral Release of Falciform Retrolental Adhesion by Scleral Buckling in Familial Exudative Vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) can often present with retinal falciform folds, and rarely with retrolenticular adhesive radial retinal folds. Management of advanced FEVR-associated tractional falciform folds with retrolenticular adhesion to the peripheral retina in the literature has been limited to vitrectomy with or without lensectomy. The authors describe a unique surgical management of a case of bilateral FEVR-associated tractional radial folds with nonaxial retrolenticular adhesion treated with scleral buckling with deferred laser, avoiding the complications associated with vitrectomy and lensectomy on ocular development. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:594-596.].