Ditte J. Hess

Off-label use of intravitreal bevacizumab (Avastin) for salvage treatment in progressive threshold retinopathy of prematurity.

Purpose: To report the short term anatomic response of intravitreal bevacizumab (Avastin, Genentech) as salvage treatment in progressive retinopathy of prematurity (ROP) in a small series of patients. Methods: The study included five eyes of three patients with progressive ROP despite peripheral laser ablation. Patients received intravitreal injections of bevacizumab (Avastin, Genentech). RetCam (Clarity Medical Systems, Inc., Pleasanton, CA) photography and ultrasonography were used to document effect. Results: Three patients were transferred to the Bascom Palmer Eye Institute/Jackson Memorial Hospital for management of progressive ROP despite laser therapy at an outside facility. RetCam fundus photography and ultrasonography were used to document all cases. After informed consent was obtained from the parents, the patients received off-label intravitreal bevacizumab as salvage treatment. Repeat intravitreal injections of bevacizumab were utilized in several cases. The ROP stabilized allowing laser supplementation. There was varying development of tractional retinal detachments in several of the eyes but the ROP component quieted in all cases. Conclusions: Off-label use of bevacizumab appears to be useful as a salvage treatment for ROP when laser treatment is precluded. It improves dilation, quiets the disease when visibility is difficult, and temporizes the disease until laser can be supplemented.

Supraselective intra-arterial chemotherapy: evaluation of treatment-related complications in advanced retinoblastoma.

Purpose: The purpose of this study is to report the complication profile and safety evaluation of supraselective intra-arterial melphalan chemotherapy in children undergoing treatment with advanced retinoblastoma. Methods: Twelve eyes of 10 children with advanced retinoblastoma (Reese-Ellsworth Group Vb or International Classification Group D) were treated with supraselective intra-ophthalmic artery infusion of melphalan. Eleven eyes of nine children had previously failed traditional management with systemic chemotherapy and laser ablation and underwent intra-ophthalmic artery infusion of melphalan as an alternative to enucleation. Serial ophthalmic examinations, retinal photography, and ultrasonographic imaging were used to evaluate treatment regime. Results: Ophthalmic artery cannulation was successfully performed in 12 eyes of 10 patients (total 16 times). Striking regression of tumor, subretinal and vitreous seeds were seen early in each case. No severe systemic side effects occurred. Grade III neutropenia was seen in one patient. No transfusions were required. Three patients developed a vitreous hemorrhage obscuring tumor visualization. One patient developed periocular edema associated with inferior rectus muscle inflammation per orbital MRI. This same patient had scattered intraretinal hemorrhages and peripapillary cotton wool spots consistent with a Purtscher’s-like retinopathy that resolved spontaneously. At the 6-month follow-up examination, nine eyes had no evidence of tumor progression, whereas three eyes were enucleated for tumor progression. In each enucleated case, viable tumor was identified on histopathologic examination. Conclusions: Ophthalmic intra-arterial infusion with melphalan is an excellent globe-conserving treatment option in advanced retinoblastoma cases with minimal systemic side effects. Local toxicities include microemboli to the retina and choroid (1/12, 8%), vitreous hemorrhage (3/12, 25%), and myositis (1/12, 8%). Enucleation remained a definitive treatment for tumor progression in 3 of 12 eyes in this small case series with limited follow-up. Further studies are necessary to establish the role of supraselective intra-arterial melphalan chemotherapy for children with retinoblastoma.

Remote image based retinopathy of prematurity diagnosis: a receiver operating characteristic analysis of accuracy

Background/aims: Telemedicine offers potential to improve the accessibility and quality of diagnosis of retinopathy of prematurity (ROP). The aim of this study was to measure accuracy of remote image based ROP diagnosis by three readers using receiver operating characteristic (ROC) analysis. Methods: 64 hospitalised infants who met ROP examination criteria underwent two consecutive bedside procedures: dilated examination by an experienced paediatric ophthalmologist and digital retinal imaging with a commercially available wide angle camera. 410 images from 163 eyes were reviewed independently by three trained ophthalmologist readers, who classified each eye into one of four categories: no ROP, mild ROP, type 2 prethreshold ROP, or ROP requiring treatment. Sensitivity and specificity for detection of mild or worse ROP, type 2 prethreshold or worse ROP, and ROP requiring treatment were determined, compared to a reference standard of dilated ophthalmoscopy. ROC curves were generated by calculating values for each reader at three diagnostic cut-off levels: mild or worse ROP (that is, reader was asked whether image sets represented mild or worse ROP), type 2 prethreshold or worse ROP (that is, reader was asked whether image sets represented type 2 prethreshold or worse ROP), and ROP requiring treatment. Results: Areas under ROC curves ranged from 0.747–0.896 for detection of mild or worse ROP, 0.905–0.946 for detection of type 2 prethreshold or worse ROP, and 0.941–0.968 for detection of ROP requiring treatment. Conclusions: Remote interpretation is highly accurate among multiple readers for the detection of ROP requiring treatment, but less so for detection of mild or worse ROP.

Scale for Photographic Grading of Vitreous Haze in Uveitis

PURPOSE To validate a scale for grading vitreous haze in uveitis using digitized photographs and standardized scoring. DESIGN Evaluation of clinical research methodology. METHODS Calibrated Bangerter diffusion filters inducing incremental decrements of spatial contrast were placed in front of the camera lens while photographing a normal eye to simulate vitreous haze. The photographs were digitized and an ordinal scale was created from 0 (none) to 8 (highest level of opacification at which fundus details could be seen). The scale steps correspond approximately to decimal Snellen visual acuities of 1.0, 0.8, 0.4, 0.2, 0.1, 0.04, 0.02, 0.01, and 0.002, with approximately 0.3 log step between each step. For validation, digitized fundus photographs of uveitis patients were displayed on a computer monitor for comparison with the standard photos. Three observers graded the test set twice under standard conditions. Interobserver and intraobserver variability and κ values for agreement greater than chance were calculated. RESULTS Variance component analysis determined that 87.7% of the variance in grades was attributable to the test item rather than to grader or session. The intraclass correlation between graders and grading sessions varied from 0.84 to 0.91. Simple agreement within 1 grade between graders and sessions occurred in 90 ± 5.5% of gradings. κ values averaged 0.91, which is considered near perfect. CONCLUSIONS A 9-step photographic scale was designed to standardize the grading of vitreous haze in uveitis patients using fundus photographs. The scale is potentially adaptable to clinical trials in uveitis.

Intraoperative OCT of a Full-Thickness Macular Hole Before and After Internal Limiting Membrane Peeling

A child with a traumatic full-thickness macular hole was imaged perioperatively using spectral-domain optical coherence tomography (SD-OCT). Intraoperative imaging using a portable SD-OCT device equipped with a handheld probe demonstrated the full-thickness macular hole to be nearly completely closed following vitrectomy and internal limiting membrane peeling. Air was used as a tamponade agent and prone positioning was used postoperatively for 2 days. SD-OCT imaging confirmed closure of the full-thickness macular hole 5 days and 1 month postoperatively.

Clinicopathologic review of enucleated eyes after intra-arterial chemotherapy with melphalan for advanced retinoblastoma.

change if the air had direct access to the venous circulatory system. The clinical situation is further complicated by a patent foramen ovale (which is present in 23%-45% of adults, based on autopsy studies). A patent foramen ovale allows trapped air to access the arterial circulatory system through the opening between the right and left atrium. This can result in air emboli throughout the systemic arterial circulatory system, causing cerebral, cardiac, and visceral infarction, as occurred in the second case. Treatment of VAE consists of immediately flooding the operative field with fluid to stop entry of the air. Additional measures would be at the discretion of the anesthesiologist and include increasing inspired oxygen, discontinuing nitrous oxide, if it is being used, inotropic support, and aspiration of air if a right atrial catheter has been placed. Although this complication is rare, ophthalmologists should be aware that it can occur during an air/fluid exchange, especially in the setting of significant trauma. During retinal cases, the anesthesiologist may not be fully aware of maneuvers happening within the eye, and the operating surgeon may be the first to recognize this problem if a patient becomes hemodynamically unstable after an air/fluid exchange is initiated. Promptly terminating the air infusion and returning the eye to a fluid filled state may help avoid systemic morbidity.

Retinopathy of Prematurity Versus Familial Exudative Vitreoretinopathy: Report on Clinical and Angiographic Findings.

BACKGROUND AND OBJECTIVE Retinopathy of prematurity (ROP) and familial exudative vitreoretinopathy (FEVR) are classified as distinct diseases; however, emerging genetic research and fluoresce-in angiographic evidence suggest a margin of overlap between the two. PATIENTS AND METHODS This was an institutional review board-approved, retrospective case series. A literature review was performed, and medical records of all pediatric patients who underwent examination under anesthesia and laser for FEVR at the Bascom Palmer Eye Institute Pediatric Retina Service by one of the authors (AMB) from Jan. 1, 2006, to June 30, 2013, were analyzed retrospectively. RESULTS Nine infants born prematurely had fluorescein angiograms and a clinical course most consistent with FEVR. Angiographic findings included irregular sprouts of vascularization at the vascular/ avascular junction, distinct pruning of vessels, pinpoint areas of hyperfluorescence, and segmental areas of vascular leakage. CONCLUSION The authors propose a classification of ROPER (ROP vs. FEVR) to more accurately stratify these patients. Identification of this subset of patients will allow for sustained surveillance of infants with ROPER who demonstrate a continuing risk of disease activity.

Retinal detachment despite aggressive management of aggressive posterior retinopathy of prematurity.

Posterior retinopathy of prematurity (ROP) is unusual in its atypical features and its aggressive, rapidly progressive course. It is more difficult to recognize and to treat, with many of these eyes progressing to retinal detachment despite multiple treatments with laser or cryotherapy. The authors present a case of aggressive posterior ROP refractory to multiple laser treatment. This patient was successfully treated with intravitreal bevacizumab, but required repeat treatment 4 months later. The second injection with bevacizumab was followed by progression to retinal detachment requiring surgery. The patient remains stable after surgery.

Lasers for the treatment of intraocular tumors.

Lasers are used extensively in ophthalmology for a variety of conditions, including many choroidal and retinal tumors. With technologic advances, current therapy attempts not only to maximize survival with globe-salvaging treatment, but also to preserve vision. Each neoplasm has different indications for primary and adjuvant therapy, as well as differing laser treatment protocols. Additionally, there are numerous laser applications available for use, including laser photocoagulation, transpupillary thermotherapy (TTT), and photodynamic therapy (PDT). The current review outlines the basic principles of laser treatment for intraocular tumors, focusing on the indications, treatment protocols, efficacy, and safety, while also presenting the latest advances in intraocular tumor treatment.

Intraocular infections in the neonatal intensive care unit

Background The purpose of this study was to report on the incidence and treatment outcomes of endogenous endophthalmitis among newborns in the neonatal intensive care unit (NICU) of a single medical center. Methods This was a noncomparative, retrospective case series of endogenous endophthalmitis among infants at the Jackson Memorial Hospital NICU treated between March 1, 2002 and March 1, 2007. Results Of 4323 infants admitted to the NICU, seven eyes of six (0.139%) infants (two males, four females) were diagnosed with endophthalmitis during the study period. Four patients were born prematurely with a mean gestational age of 27.5 weeks and a mean birth weight of 1153 g. Retinopathy of prematurity was reported in two of the six patients. Mean follow-up was 3.5 years. The diagnosis was confirmed by positive cultures or polymerase chain reaction testing at a median age of 34 postnatal days. Positive cultures included Candida albicans (n = 4), Pseudomonas aeruginosa (n = 1), and Herpes simplex type 2 (n = 1). All patients received systemic treatment and five received adjunctive ophthalmic interventions, including intravitreal antibiotics in five eyes of four patients and vitrectomy with pars plana lensectomy in three eyes. One patient underwent primary enucleation and another had delayed evisceration. In the remaining five eyes, there was a normal appearing posterior segment and normal intraocular pressures at last follow-up. Conclusion Endogenous endophthalmitis is a rare complication in infants in the NICU, but may occur in patients with candidemia, bacteremia, retinopathy of prematurity, and low birth weight. Despite early and appropriate treatment, involved eyes may have poor outcomes.