In Situ Tremor in Vitreoretinal Surgery.

OBJECTIVE: Surgeon tremor was measured during vitreoretinal microscopic surgeries under different hand support conditions. BACKGROUND: While the ophthalmic surgeon's forearm is supported using a standard symmetric wrist rest when operating on the patient's same side as the dominant hand (SSD), the surgeon's hand is placed directly on the patient's forehead when operating on the contralateral side of the dominant hand (CSD). It was hypothesized that more tremor is associated with CSD surgeries than SSD surgeries and that, using an experimental asymmetric wrist rest where the contralateral wrist bar gradually rises and curves toward the patient's operative eye, there is no difference in tremor associated with CSD and SSD surgeries. METHODS: Seventy-six microscope videos, recorded from three surgeons performing macular membrane peeling operations, were analyzed using marker-less motion tracking, and movement data (instrument path length and acceleration) were recorded. Tremor acceleration frequency and magnitude were measured using spectral analysis. Following 47 surgeries using a conventional symmetric wrist support, surgeons incorporated the experimental asymmetric wrist rest into their surgical routine. RESULTS: There was 0.11 mm/s2 (22%) greater (p = .05) average tremor acceleration magnitude for CSD surgeries (0.62 mm/s2, SD = 0.08) than SSD surgeries (0.51 mm/s2, SD = 0.09) for the symmetric wrist rest, while no significant (p > .05) differences were observed (0.57 mm, SD = 0.13 for SSD and 0.58 mm, SD = 0.11 for CSD surgeries) for the experimental asymmetric wrist rest. CONCLUSION: The asymmetric wrist support reduced the difference in tremor acceleration between CSD and SSD surgeries.

Response to aflibercept as secondary therapy in patients with persistent retinal edema due to central retinal vein occlusion initially treated with bevacizumab or ranibizumab.

BACKGROUND: Recent advances have given practitioners options for the treatment of macular edema secondary to central retinal vein occlusion. These options include steroid injections and implants as well as anti-vascular endothelial growth factor medications. However, there is little in the medical literature to guide secondary therapy when an initial treatment strategy is insufficient. The authors present encouraging results from the treatment of six consecutive cases of central retinal vein occlusion treated with aflibercept as a secondary therapy for macular edema refractory to repeated intravitreal bevacizumab or ranibizumab injections. METHODS: A retrospective review of six consecutive cases of central retinal vein occlusion with persistent macular edema despite regular anti-vascular endothelial growth factor injections that were transitioned to aflibercept was conducted. Optical coherence tomography and visual acuity data were examined. RESULTS: All six eyes from the six patients included showed either complete or near complete resolution of macular edema with one or two injections of aflibercept. The improvement in edema was accompanied by lasting modest visual gains in three of the six patients and in subjective visual improvement in four of the six patients. CONCLUSION: The six eyes in this series all responded favorably to aflibercept as a secondary therapy. Although the sample size is too small to draw definitive conclusions, the results are encouraging.

NONSURGICAL RESOLUTION OF FULL-THICKNESS MACULAR HOLES WITHOUT VITREOMACULAR TRACTION.

BACKGROUND/PURPOSE: The purpose of this study was to report a case series of full-thickness macular holes without vitreomacular traction that resolved without surgery. METHODS: This study is a retrospective case series of 11 patients who demonstrated closure of full-thickness macular holes without surgical intervention. RESULTS: All full-thickness macular holes closed, with all patients having improvement in visual acuity. All but one of the cases had visual acuity better than 20/40 at last recorded visit. Most cases presented with associated epiretinal membrane (73%), cystoid changes (64%), defects <150 µ m (80%), and resolved within 2 months (91%). Topical anti-inflammatory drops were used in 7 of 11 cases, and dorzolamide was used in one case. CONCLUSION: Full-thickness macular holes can develop in eyes without the presence of vitreomacular traction. Topical therapy without vitrectomy may be particularly helpful in closure of full-thickness macular holes with associated cystoid macular edema. Holes with a lamellar hole component may spontaneously resolve as part of a retinal remodeling process.

Intratarsal epidermal inclusion cyst.

PURPOSE: To report 3 cases of epidermal inclusion cyst that arose within the tarsus, an unusual site of origin. METHODS: A retrospective review of medical records of patients undergoing excision of eyelid epidermal inclusion cysts by one surgeon (MJL) over a decade revealed 3 cases of intratarsal epidermal inclusion cyst. Initially, these lesions resembled chalazia and were first addressed with incision and curettage. There was recurrence of the cyst in all the 3 cases from 1 to 4 months, and subsequent complete excision was necessary. RESULTS: At surgery in each of these cases a cyst arising within the tarsus was encountered. Eventually, the tarsus containing the base of the cyst was excised to ensure complete removal. The cysts were approximately 8 mm to 10 mm in greatest dimension and had yellowish-white gelatinous contents. Histopathologic evaluation revealed keratin-filled cysts arising from tarsus and lined by stratified keratinized epithelium. In one of the cases the tarsal tissue around the cyst wall showed epidermal elements presumably derived from sebaceous gland. There have been no recurrences after complete excision (follow-up range, 9-60 months). CONCLUSIONS: Intratarsal epidermal inclusion cysts share some clinical features with chalazia. Lack of inflammation, lack of fluctuation in size, gradual continued slow growth, and delayed onset of recurrence may help to differentiate tarsal cyst from recurrent chalazion. Incision and curettage, however, is not effective long-term treatment for this entity. Total excision of the cyst including full-thickness excision of tarsus at the cyst's base of origin is suggested for definitive treatment.

Propranolol for Proliferative Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To determine the effect of propranolol on retinal neovascularization due to proliferative diabetic retinopathy (PDR). PATIENTS AND METHODS: For this prospective pilot, interventional, case series, patients with diabetes with PDR (n = 10 subjects; 12 eyes) were recruited at the ophthalmology clinic of the University of Wisconsin - Madison. Subjects were administered oral propranolol for 12 weeks and retinopathy and area of retinal neovascularization were monitored with fundus photography and fluorescein angiography (FA). The study's main outcome measures were photographic area of retinal neovascularization and degree of leakage on FA. RESULTS: All eyes demonstrated stable degrees of retinal neovascularization by the end of 12 weeks. CONCLUSION: This dose of oral propranolol during a period of 12 weeks did not demonstrate significant effect on retinal neovascularization due to PDR. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:35-40.].

Clinicopathologic correlation of explanted AlphaCor artificial cornea after exposure of implant.

PURPOSE: To describe the clinical presentation and histopathologic findings in a case of explantation of an AlphaCor artificial cornea implant caused by exposure of the skirt. METHODS: We describe the case report of a 46-year-old man who suffered trauma to the right eye, resulting in 4 failed penetrating keratoplasties (PKPs). Subsequently, an AlphaCor implantation was performed with some visual improvement. Slightly more than 2 years after the implant, skirt exposure occurred, possibly secondary to infectious keratitis in an area of a ruptured bulla, and explantation was performed. Corneal stability was established with repeat corneal transplantation. RESULTS: Histopathologic evaluation of the surgical specimen revealed chronic nongranulomatous inflammation and fibrosis in the peripheral skirt, indicating that biointegration was maintained. However, peripheral corneal stromal melting led to skirt exposure. Focal calcification, as well as retroprosthetic membrane formation, was also identified. CONCLUSIONS: The AlphaCor implant is a viable method of treatment for multiple failed PKPs, but it may be associated with unique complications, including corneal stromal melting, focal calcification, and retroprosthetic membrane formation. Infectious keratitis may be a risk factor for corneal stromal melting and needs to be managed aggressively. Explantation of the implant is essential if the skirt is exposed.

Ocular changes after photodynamic therapy.

PURPOSE: The aim of this study was to identify the changes in the primate visual system after a single session of photodynamic therapy (PDT) in an intact nonhuman primate retina. METHODS: As part of a larger study, PDT (wavelength 689 nm, 50 J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2 intravenous infusion) was performed in one eye each of two cynomolgus monkeys. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICG), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) were performed at baseline and 12 time points (1-283 days) after PDT. In addition, retinal histopathologic findings were evaluated at 9 months. RESULTS: Various morphologic changes, including whitening of the treated area, RPE proliferation, closure of the choroidal vasculature, and subretinal edema (followed by foveolar thinning) were observed. Most of the changes persisted and were detectable in histopathologic evaluation at 9 months. Reductions of the mfERG amplitude, followed by varying degrees of recovery from the treated and the border regions, were observed. This was accompanied by progressive delay of P1 peak time up to 3 months after treatment, followed by complete recovery at 9 months. In addition, the nontreated area showed amplitude and timing mfERG deficits, which underwent gradual (but not complete) recovery. CONCLUSIONS: In a primate model, under standard clinical parameters, a single PDT treatment resulted in various dynamic morphologic and functional retinal changes detectable for up to 9 months after treatment. The significance of the observed changes and possible ways of pharmacologic interference with PDT adverse effects are discussed.

Outcomes associated with ganciclovir implants in patients with AIDS-related cytomegalovirus retinitis.

PURPOSE: To investigate complications associated with ganciclovir implants used to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors that predict poor outcomes. DESIGN: Retrospective chart review. PARTICIPANTS: Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities who underwent implantation procedures during the period January 1, 1995 through December 31, 2001. METHODS: Baseline for each patient was the date of the first implantation procedure performed during the study period by one of the facilities' surgeons (index implant). Medical and ophthalmological data were collected at baseline and at specific time points after baseline. The dates on which additional implantation procedures were performed and the dates on which complications or vision loss were identified were also recorded. Relationships between potential risk factors and outcomes were studied by Kaplan-Meier analyses and Cox proportional hazards regression models. MAIN OUTCOME MEASURES: Primary outcome measures included postoperative complications specifically related to or possibly related to ganciclovir implants. A secondary outcome measure was vision loss after implantation procedures. RESULTS: The charts of 174 patients (one study eye per patient; 279 implants) were reviewed. Median follow-up was 14.4 months (range, 0-7 years). Complications specifically related to implants occurred throughout follow-up at a rate of 0.064 events per patient-year. Complications possibly related to implants occurred at an overall rate of 0.377 per patient-year, but seemed to be more common during the first 2 years after baseline. During the first 2 years of follow-up, retinal detachments occurred at a rate of 0.156 events per patient-year. The cumulative risk of vision loss (> or =3 lines of Snellen visual acuity) at 7 years was 70%. Poor outcomes were associated with disease factors (size and activity of lesions), lack of highly active antiretroviral therapy (HAART), and lack of HAART-associated immune reconstitution, but not with surgical factors or implant-specific complications. CONCLUSIONS: Complications specifically associated with ganciclovir implants can occur many years after implantation procedures, but the incidence of such complications is low. Continued vision loss is not attributable directly to complications of implants in most cases. This information will help in planning of treatment strategies for CMV retinitis in long-term survivors of human immunodeficiency virus disease.

Wet age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in industrialized nations for those age 65 and above. The majority of patients with severe visual loss suffer from the wet form of AMD wherein there is choroidal neovascularization (CNV) and associated manifestations such as retinal pigment epithelial detachment, subretinal hemorrhages, and fibrovascular disciform scarring. The main focus on understanding the pathogenesis of CNV has been on the hypothesis that the diffuse thickening of Bruch's membrane predisposes it to develop cracks and in-growth of new vessels from choriocapillaries with associated low-grade inflammatory response. Currently, three types of treatments (laser photocoagulation, photodynamic therapy, and anti-Vascular Endothelial Growth Factor (VEGF) therapy) have been demonstrated to limit or delay loss of vision in patients. Only a minority of cases show stabilization of vision and a small proportion of cases show significant improvement in vision. This highlights the need for more and better pharmacologic or other interventions, with the goal of lowering recurrence rates and preventing the development of CNV in order to achieve better functional outcomes.

Vogt-Koyanagi-Harada syndrome with intracranial meningioma: an as yet unreported association.

CASE REPORT: We document a previously unreported association of Vogt-Koyanagi-Harada (VKH) syndrome with intracranial meningioma. A female patient with diminished vision, exudative retinal detachment, and headache was diagnosed with VKH syndrome, more precisely a Harada form of disease with intracranial meningioma, on the basis of exudative retinal detachment, typical fundus fluorescein findings, and magnetic resonance imaging. With intravenous steroid therapy, visual acuity improved and the detachment settled within a week. At 3 months, the detachment recurred but improved after retreatment. At 1 year, the tumour was unchanged in size. COMMENTS: VKH syndrome may be associated with intracranial meningioma that may affect the patient's overall morbidity or mortality.

Diabetic macular edema: therapeutic options.

Treatment for diabetic macular edema (DME) is continuously evolving with the advent of pharmacologic therapies. Focal laser photocoagulation remains the historical standard of care; however, a new wave of studies is rapidly emerging that shows the benefit of intravitreal antivascular endothelial growth factor medications and corticosteroids. The goal of this review is to compare the various treatment options for DME, and include data from the most recent clinical trials of therapies for this complex condition.

A study of histopathological features of latanoprost-treated irides with or without darkening compared with non-latanoprost-treated irides.

OBJECTIVES: To study the histopathological features of latanoprost-treated irides with or without darkening, compared with non-latanoprost-treated irides. METHODS: Iridectomy specimens and patient history forms were independently examined by 3 ophthalmic pathologists in a masked fashion. Specimens were evaluated for premalignant changes and for differences in level of pigmentation and degrees of cellularity, inflammation, and vascular abnormalities. RESULTS: The specimens consisted of 22 latanoprost-treated darkened irides, 35 latanoprost-treated irides without darkening, and 35 non-latanoprost-treated irides. There was a statistically significant decrease in the number of nuclear invaginations and prominent nucleoli in latanoprost-treated darkened irides compared with the other 2 groups (P = .004 and P = .005, respectively). The average thickness and pigmentation of the anterior border layer was greater in the latanoprost-treated darkened irides than in the other 2 groups (P = .03 and P = .02, respectively). The latanoprost-treated darkened irides had increased pigmentation of the stroma (P < .001), stromal fibroblasts (P < .001), melanocytes (P = .005), vascular endothelium (P = .02), and adventitia (P < .001) relative to the other 2 groups. CONCLUSIONS: There is no histopathological evidence of premalignant changes in latanoprost-treated darkened irides. The latanoprost-induced iris color changes are due to a thickening of the anterior border layer and an increased amount of melanin in the anterior border layer and within the stromal melanocytes.

1 alpha-Hydroxyvitamin D2 inhibits growth of human neuroblastoma.

Neuroblastoma is the most common extracranial solid tumor in childhood. The poor outcomes of patients with high-risk neuroblastoma have encouraged the search for new therapies. In the current study, the effect of the vitamin D analog 1alpha-hydroxyvitamin D2 (1alpha-OH-D2, doxercalciferol) was assessed in a mouse xenograft model of human neuroblastoma. Vitamin D receptor (VDR) expression levels in seven neuroblastoma cell lines were compared using real-time PCR. SK-N-AS cells, which express relatively high levels of VDR, were injected into the flanks of 60 mice. The mice were treated daily via oral gavage for 5 weeks with vehicle (control), 0.15 microg, or 0.3 microg of 1alpha-OH-D2. The animals were then euthanized, and tumors, sera, and kidneys were collected and analyzed. End tumor volumes were significantly smaller in both the 0.15 microg group (712.07 mm3, P = 0.0121) and 0.3 microg group (772.97 mm3, P = 0.0209) when compared to controls (1,681.75 mm3). In terms of toxicity, serum calcium levels were increased but mortality was minimal in both treatment groups. These results were similar to those previously described in the transgenic (LHbeta-Tag) and human xenograft (Y-79) models of retinoblastoma, a related tumor. In vitro cell viability studies of SK-N-AS and NGP cells, which represent two major human neuroblastoma subtypes that differ in their genetic abnormalities as well as their VDR expression levels, show that both are sensitive to calcitriol, the active metabolite of vitamin D3. In conclusion, the present study shows that 1alpha-OH-D2 can inhibit human neuroblastoma growth in vivo with relatively low toxicity. The safety of 1alpha-OH-D2 has been extensively studied; the drug is FDA-approved for the treatment of adult kidney patients, and Phase I/II trials have been conducted in adult oncology patients. There should not be major obstacles to starting Phase I and II clinical trials with this drug in pediatric patients with high-risk neuroblastoma.