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Biomedical subjects

Michael T Trese

Publications and source records attributed to Michael T Trese.

At least 19 recordsLinked to original sources

Proceedings of the Third International Symposium on Retinopathy of Prematurity: an update on ROP from the lab to the nursery (November 2003, Anaheim, California).

The Third International Symposium on Retinopathy of Prematurity (ROP) was convened with the aim of cross fertilizing the horizons of basic and clinical scientists with an interest in the pathogenesis and management of infants with ROP. Ten speakers in the clinical sciences and ten speakers in the basic sciences were recruited on the basis of their research to provide state of the art talks. The meeting was held November 9, 2003 immediately prior to the American Academy of Ophthalmology meeting; scholarships were provided for outreach to developing countries and young investigators. This review contain the summaries of the 20 platform presentations prepared by the authors and the abstracts of presented posters. Each author was asked to encapsulate the current state of understanding, identify areas of controversy, and make recommendations for future research. The basic science presentations included insights into the development of the human retinal vasculature, animal models for ROP, growth factors that affect normal development and ROP, and promising new therapeutic approaches to treating ROP like VEGF targeting, inhibition of proteases, stem cells, ribozymes to silence genes, and gene therapy to deliver antiangiogenic agents. The clinical presentations included new insights into oxygen management, updates on the CRYO-ROP and ETROP studies, visual function in childhood following ROP, the neural retina in ROP, screening for ROP, management of stage 3 and 4 ROP, ROP in the third world, and the complications of ROP in adult life. The meeting resulted in a penetrating exchange between clinicians and basic scientists, which provided great insights for conference attendees. The effect of preterm delivery on the normal cross-talk of neuroretinal and retinal vascular development is a fertile ground for discovering new understanding of the processes involved both in normal development and in retinal neovascular disorders. The meeting also suggested promising potential therapeutic interventions on the horizon for ROP.

Humans↗

Retinopathy of prematurity: the life of a lifetime disease.

PURPOSE: To provide information on retrolental fibroplasias (RLF), later known as retinopathy of prematurity. DESIGN: Review of the literature on the subject and a first-person account of what was then RLF by one of the authors (A.P.) who was involved in the earliest days in research regarding RLF. METHODS: MEDLINE search on the topics of RLF and retinopathy of prematurity plus a first-person historic review of original work that dealt with RLF. RESULTS: In 1942, elevated levels of oxygen were thought to play a major role in the development of the disease; at that time, no treatment was available. During the lifetime of this disease, other possible causes have been investigated. These include vitamin E as a prophylaxis against retinopathy of prematurity and the efficacy of light reduction to prevent retinopathy of prematurity. It has been shown that the light reduction does not play a role in reducing the progression of retinopathy of prematurity. Vitamin E studies were inconclusive; some studies show a positive effect and others do not. A major advance occurred with the development of the International Classification of Ophthalmology in 1984, which laid the groundwork for collaborative studies to determine whether cryotherapy of the avascular zone of retina would reduce the incidence of blindness in newborn infants, when compared with control subjects. The study showed that cryotherapy was effective; this was followed by laser photocoagulation when lasers became portable enough to take to the neonatal intensive care unit. At the same time, improved surgical techniques moved from scleral buckling for retinal detachment to vitrectomies (some lens sparing) for more desperate cases that had progressed to stage 4 and stage 5 retinopathy of prematurity. Late changes in adults who were born before any treatment and are now baby boomers ran the gamut from the dragging of the retina in the posterior pole to retinal detachment, cataract, and myopia. CONCLUSION: Retinopathy of prematurity is a lifetime disease for which preventive and better treatment modalities continue to evolve.

Animals↗

Spontaneous resolution of traumatic macular hole-related retinal detachment.

PURPOSE: To report a case of spontaneous resolution of traumatic macular hole-related retinal detachment. DESIGN: Observational case report. METHODS: Clinical examination and optical coherence tomographic (OCT) evaluation of a patient who experienced spontaneous resolution of a retinal detachment resulting from a traumatic macular hole. RESULTS: A 12-year-old boy developed a macular hole and retinal detachment after blunt ocular trauma. Spontaneous reattachment of the retina and closure of the macular hole were documented at clinical examination and by OCT three weeks after presentation. CONCLUSIONS: Spontaneous closure of traumatic macular hole and resolution of associated retinal detachment can occur.

Child↗

Optical coherence tomography findings in stage 4A retinopathy of prematurity: a theory for visual variability.

PURPOSE: To report macular anatomic abnormalities in eyes with stage 4A retinopathy of prematurity (ROP) that may account for poor visual outcome despite an ophthalmoscopically normal-appearing posterior pole. DESIGN: Retrospective case series. PARTICIPANTS: Nine patients (14 eyes). METHODS: Nine patients (14 eyes) diagnosed with stage 4A retinal detachments were imaged with optical coherence tomography (OCT) before repair by lens-sparing pars plana vitrectomy. One patient (2 eyes) 2 years after successful lens-sparing vitrectomy for stage 4A detachment with reduced visual acuity underwent fluorescein angiography, fundus photography, and imaging with OCT. MAIN OUTCOME MEASURE: Optical coherence tomography findings. RESULTS: Preoperative OCT confirmed absence of macular involvement in 12 of 14 eyes. Two eyes demonstrated diffuse intraretinal posterior pole changes. Both eyes of a 2-year-old infant demonstrated a lack of normal foveal architecture on OCT scanning and an absent foveal avascular zone on angiography. CONCLUSIONS: Anatomic macular abnormalities--not immediately apparent ophthalmoscopically--may explain the variability in visual outcome after lens-sparing vitrectomy for stage 4A ROP.

Diagnostic Techniques, Ophthalmological↗

Genetic evaluation to establish the diagnosis of X-linked familial exudative vitreoretinopathy.

PURPOSE: To determine the usefulness of genetic analysis for confirming the diagnosis of X-linked familial exudative vitreoretinopathy (FEVR) and verifying the mode of inheritance. METHODS: Twenty-seven consecutive patients diagnosed with FEVR were enrolled for genetic analysis. All patients underwent dilated fundus examination. A complete birth, medical, and family history was obtained at the time of examination. Patients were categorized by gender and family history in an effort to identify X-linked FEVR. Participants provided a blood sample for analysis and were evaluated for a mutation in the Norrie's disease gene (NDP) by direct sequencing. RESULTS: Of the 27 enrolled patients, four male patients had a pedigree consistent with X-linked inheritance and 12 male patients had little or no family history. Two of these 16 patients were found to have a missense mutation in the NDP gene. CONCLUSIONS: We found genetic testing of NDP to be helpful in confirming the diagnosis of X-linked FEVR in male patients, especially when limited family history was available. As genetic diagnostics improve, we feel that confirming diagnoses and informing patients better through genetic evaluation and consultation will become more useful in the clinical practice of ophthalmology.

DNA Mutational Analysis↗

Intraschisis cavity fluid composition in congenital X-linked retinoschisis.

PURPOSE: To describe the intraschisis cavity protein composition in congenital X-linked retinoschisis (CXLRS) from two eyes of one child. METHODS: The authors present a child with complex, Type 3 CXLRS who underwent bilateral surgical repair with autologous plasmin enzyme-assisted lens-sparing vitrectomy. Undiluted samples of intraschisis fluid and vitreous fluid from two eyes (one child) were obtained and used for protein analysis. RESULTS: The patient underwent successful schisis repair with plasmin-assisted lens-sparing vitrectomy and silicone oil. Two unique protein bands were identified in the intraschisis cavity sample of each eye by gel electrophoresis. The proteins were identified as tenascin-C, an extracellular matrix protein involved in wound healing, and cystatin C, a ubiquitous cysteine protease inhibitor implicated in inflammation. CONCLUSIONS: Tenascin-C has previously been described in its complex relationship with decorin and fibronectin in normal wound healing. Tenascin's upregulation in sites of inflammation and tenascin's role as an antiadhesive molecule may contribute to the pathogenesis of CXLRS. To the authors' knowledge, this is the first description of intraschisis cavity fluid.

Biomarkers↗

Posterior hyaloid contracture in pediatric vitreoretinopathies.

BACKGROUND: Retinal detachment in pediatric vasoproliferative disorders such as retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) have an exudative and tractional component. Younger eyes have an especially adherent posterior hyaloid. Contraction of the posterior hyaloid interface may lead to tractional retinal detachment. METHODS: Retrospective chart review of six eyes (four ROP, two FEVR) with diffuse contraction of the posterior hyaloid resulting in retinal detachment. Fundus photographs and optical coherence tomography findings (one eye) are presented. RESULTS: Diffuse proliferation along the posterior hyaloid required extensive lamellar dissection at times aided by autologous plasmin enzyme. A diffuse, taut posterior hyaloid resulted in marked tractional component to retinal detachment. CONCLUSIONS: Recognition of hyaloid contracture will aid in the proper diagnosis and surgical planning and repair of eyes with pediatric vasoproliferative disorders.

Adolescent↗

Congenital X-linked retinoschisis classification system.

PURPOSE: To establish a classification system for congenital X-linked retinoschisis (CXLRS) using clinical examination and optical coherence tomography (OCT). METHODS: Thirty-eight eyes of 19 patients who carried a clinical diagnosis of CXLRS were examined with OCT and clinical examination. Eyes were classified into one of four types based on a combination of clinical examination and OCT. RESULTS: All patients had bilateral OCT scanning performed at an average age of 8.64 years (range 2.24-17.4 years). Review of OCT scans revealed that 37 of 38 eyes had foveal schisis (97%) while 31 of 38 (82%) eyes had macular schisis deeper than the nerve fiber layer in areas of ophthalmoscopically normal macular retina. The authors termed this flat schisis phenomenon lamellar schisis. Thirty of 38 (79%) had peripheral bullous schisis cavities present. CONCLUSIONS: OCT examinations of patients with CXLRS reveal lamellar schisis in areas of ophthalmoscopically normal macular retina in 82% of eyes with the clinical diagnosis of CXLRS. Using both clinical examination and OCT, the authors were able to identify foveal, lamellar, and peripheral schisis, lamellar schisis only identifiable by OCT. These findings allow the authors to propose a classification system. The authors hope this classification system will allow a better understanding of the natural history of CXLRS disease and allow testing of therapeutic options.

Adolescent↗

The Photographic Screening for Retinopathy of Prematurity Study (Photo-ROP): study design and baseline characteristics of enrolled patients.

OBJECTIVE: The Photographic Screening for Retinopathy of Prematurity Study (Photo-ROP) sought to evaluate the utility of digital wide-angle photographic fundus screening for retinopathy of prematurity (ROP) as compared to bedside indirect ophthalmoscopy. This article describes the study design and presents baseline characteristics of the subjects. DESIGN: Prospective, multicenter, masked, Internet-based clinical trial. PARTICIPANTS: Premature infants <31 weeks postmenstrual age at birth and <1000 g birthweight. INTERVENTIONS: Examinations began at 31 weeks postmenstrual age or 4 weeks postnatal age, whichever was later. Both eyes of all infants were imaged with a panoramic fundus imaging system followed by indirect ophthalmoscopic fundus examination. Images were transmitted via Internet to the Reading Center for interpretation by masked graders. Clinical interpretations based on indirect ophthalmoscopy were recorded for comparison with the Reading Center determinations. Examinations were performed weekly for 10 weeks or until an infant was discharged from the hospital. MAIN OUTCOME MEASURE: Sensitivity, specificity, and positive and negative predictive values of Reading Center image interpretations were compared to clinical impressions based on bedside indirect ophthalmoscopy. RESULTS: Enrollment began in February 2001 and was completed in February 2002. The target number of infants was 50, and 62 were enrolled. Of those enrolled, 51 infants (102 eyes) were considered eligible, and are the subject of this article. Mean postmenstrual age (+/- SD) at time of delivery was 26.80 +/- 1.73 weeks (median = 26.86 weeks, interquartile range [IQR] = 2.43 weeks). Mean postmenstrual age at first examination (+/- SD) was 32.19 +/- 2.86 weeks (median = 31.71 weeks, IQR = 2.29 weeks). Mean birthweight (+/- SD) was 830.51 +/- 219.57 g (median = 817 g, IQR = 225 g). Female infants comprised 49.02% of the patients. Race distribution was as follows: white 45.10%, African or black 39.22%, Hispanic 3.92%, Asian 9.80%, and other races 1.96%. Mean follow-up (+/- SD) was 5.73 +/- 3.22 weeks (median = 6 weeks, IQR = 5, range = [1, 15]). CONCLUSIONS: The Photo-ROP Study Cooperative Group successfully recruited and enrolled at-risk premature infants into a longitudinal, prospective clinical trial comparing two different diagnostic approaches. Technology employed in this study is comparable to that currently available. Design issues for this trial included establishing the information technology infrastructure for an ROP study based on digital imaging, defining the study endpoints, estimating event rates, defining a standardized imaging protocol, and defining standards for interpretation of image quality and clinical findings.

Canada↗

Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5.

Familial exudative vitreoretinopathy (FEVR) is a hereditary eye disorder that affects both the retina and vitreous body. Autosomal recessive FEVR was diagnosed in multiple individuals from three consanguineous families of European descent. A candidate-locus-directed genome scan shows linkage to the region on chromosome 11q flanked by markers D11S905 and D11S1314. The maximum LOD score of 3.6 at theta =0 is obtained with marker D11S987. Haplotype analysis confirms that the critical region is the 22-cM (311-Mb) interval flanked by markers D11S905 and D11S1314. This region contains LRP5 but not FZD4; mutations in both of these genes cause autosomal dominant FEVR. Sequencing of LRP5 shows, in all three families, homozygous mutations R570Q, R752G, and E1367K. This suggests that mutations in this gene can cause autosomal recessive as well as autosomal dominant FEVR.

Base Sequence↗

Visual outcomes after lens-sparing vitrectomy for stage 4A retinopathy of prematurity.

PURPOSE: To assess the visual outcomes of patients with stage 4A retinal detachments (RDs) from retinopathy of prematurity (ROP). DESIGN: Retrospective review of a consecutive case series of children referred to the pediatric retina service of Associated Retinal Consultants, Royal Oak, Michigan. PARTICIPANTS: Forty-five eyes of 39 children. METHODS: The stage of RD for each patient was determined during an examination under anesthesia. All patients underwent a lens-sparing pars plana vitrectomy (PPV) with membrane peeling. Postoperative anatomic status was determined by ophthalmoscopy either during an office examination or during an examination under anesthesia. Visual outcomes were ascertained by consulting pediatric ophthalmologists using either Teller or Allen acuities. MAIN OUTCOME MEASURES: Anatomic and visual outcomes. RESULTS: Formalized visual acuity (VA) measurement was performed in 23 eyes of 20 children, and was not performed in 22 eyes of 19 children. All 23 eyes that were formally tested had successful retinal reattachment. The macula appeared to be normal and without distortion in 19 of 23 eyes (83%) during the follow-up period. Average logarithm of the minimum angle of resolution VA was 20/58. Three eyes had acuities of 20/200, and 4 had acuities of 20/100. All other eyes were 20/80 or better. Average age at time of VA was 3.51 years. CONCLUSIONS: Patients with ROP and stage 4A RDs can be treated successfully with respect to anatomic and visual outcome utilizing lens-sparing PPV.

Gestational Age↗

Vitrectomy for chronic macular holes.

PURPOSE: To address the efficacy of surgical intervention for chronic macular holes. METHODS: The cases of 22 patients (23 eyes) who underwent pars plana vitrectomy with or without internal limiting membrane (ILM) peeling and use of 10% to 16% C3F8 gas for macular holes of duration of >1 year (mean, 4.2 years; range, 1.2-15 years) were retrospectively reviewed. Preoperative visual acuity ranged from 20/60 to 5/200 (mean, 20/278). Thirteen eyes (56.5%) had stage 3 macular holes, and 10 eyes (43.5%) had stage 4 macular holes. The mean age of the patients was 70.2 years (range, 47-78 years), and 20 (87%) were female. RESULTS: Nineteen (83%) of 23 macular holes were closed at final follow-ups at >/=9 months (mean, 4.67 years; range, 0.9-10.8 years). With one operation that included ILM peeling, 13 (81%) of 16 eyes had holes that closed. Seven eyes on which initial surgery without ILM peeling failed underwent reoperation with ILM peeling, and all but one had closed holes. ILM peeling was significant for surgical success of one operation (Fisher exact test, P = 0.0005). Postoperative visual acuity ranged from 20/30 to 20/800 (mean, 20/166). Improved vision with halving of the visual angle occurred in 16 eyes (70%). Nine eyes (39%) achieved visual acuity of 20/70 or better, and two eyes (8.7%) achieved visual acuity of 20/40 or better. One eye (4%) had worse visual acuity, and three eyes (13%) remained unchanged. Cataract was a possible cause of decreased vision in six eyes (26%) at the end of follow-up. CONCLUSION: Chronic macular holes can be surgically closed with visual improvement in most patients. ILM peeling is an important surgical factor for closure of the macular hole with one operation.

Aged↗

Evolving guidelines for intravitreous injections.

Intravitreous (i.v.t.) injection is increasingly being incorporated into the management of ocular diseases. While only fomivirsen sodium (Vitravene) is currently approved by the Food and Drug Administration as an i.v.t. injection, the number of approved i.v.t. injections indications is anticipated to grow on the basis of promising results from ongoing clinical studies. Despite the potential benefits that may be derived from intraocular injections of different agents, no guidelines have been published previously for i.v.t. injection. The purpose of this document is to identify specific strategies for the delivery of i.v.t. injection that may reduce risks and improve outcomes. Consensus was sought among a panel of investigators, surgeons experienced with this technique, and industry representatives. Objective evidence was sought for all guidelines, but consensus was accepted where evidence remains incomplete. In the absence of either evidence or consensus, the current manuscript identifies outstanding issues in need of further investigation. It is anticipated that more complete guidelines will evolve over time, potentially altering some of the guidelines included here, based on new applications of i.v.t. injection, additional clinical experience, and results of clinical trials.

Humans↗

Overproduction and partial purification of the Norrie disease gene product, norrin, from a recombinant baculovirus.

Abnormal vascularization of the peripheral retina and retinal detachment are common clinical characteristics of Norrie disease (ND), familial exudative vitreoretinopathy, Coats' disease, and retinopathy of prematurity. Although little is known about the molecular basis of these diseases, studies have shown that all of these diseases are associated with mutations in the ND gene. In spite of this, little is known about norrin, its molecular mechanism of action, and its functional relationship with the development of abnormal retinal vasculature. To obtain a large quantity of norrin for structural and functional studies, we have overproduced it in insect cells. For this purpose, a cDNA fragment (869 bp) was isolated from a human retinal cDNA library by amplification and was cloned into an expression vector. The purified plasmid was co-transfected with wild-type linearized Bac-N-Blue DNA into S. frugiperda Sf21 insect cells. The recombinant virus plaques were purified and clones were selected based on the level of recombinant protein expressed in Sf21 cells infected with a purified recombinant virus. From these, a high-titer stock was generated and subsequently used to prepare a fused protein on a large scale. The protein was partially purified by the process of immobilized metal affinity chromatography and the use of ion exchange chromatography

Abnormalities, Multiple↗

Congenital blindness and osteoporosis-pseudoglioma syndrome.

Isteoporosis-pseudoglioma syndrome (OPPG) is a rare heritable entity that features severe osteoporosis and many variable ophthalmic findings leading to congenital or juvenile blindness. These include microphthalmos, cataracts, bilateral pseudogliomatous retinal detachments, and phthisis bulbi. OPPG is usually not suspected until fractures occur, frequently after seemingly minor trauma. We report the ophthalmic findings of an infant girl with OPPG.

Arthrography↗