Intravitreal drug delivery in retinal disease: are we out of our depth?

INTRODUCTION: With the ever-increasing global burden of retinal disease, there is an urgent need to vastly improve formulation strategies that enhance posterior eye delivery of therapeutics. Despite intravitreal administration having demonstrated notable superiority over other routes in enhancing retinal drug availability, there still exist various significant physical/biochemical barriers preventing optimal drug delivery into the retina. A further complication lies with an inability to reliably translate laboratory-based retinal models into a clinical setting. Several formulation approaches have recently been evaluated to improve intravitreal therapeutic outcomes, and our aim in this review is to highlight strategies that hold the most promise. AREAS COVERED: We discuss the complex barriers faced by the intravitreal route and examine how formulation strategies including implants, nanoparticulate carriers, viral vectors and sonotherapy have been utilized to attain both sustained delivery and enhanced penetration through to the retina. We conclude by highlighting the advances and limitations of current in vitro, ex vivo and in vivo retinal models in use by researchers globally. EXPERT OPINION: Various nanoparticle compositions have demonstrated the ability to overcome the retinal barriers successfully; however, their utility is limited to the laboratory setting. Optimization of these formulations and the development of more robust experimental retinal models are necessary to translate success in the laboratory into clinically efficacious outcomes.

Snoring is associated with unexpected patient head movement during monitored anesthesia care vitreoretinal surgery.

PURPOSE: To assess whether snoring is associated with sudden patient movement during local anesthesia with intravenous sedation. METHODS: In this prospective cohort study, patients undergoing ocular surgery with local anesthesia with intravenous sedation were studied. The occurrence or absence of snoring, and whether patient movement was noted were prospectively recorded. Complications that arose from patient movement were also noted. RESULTS: A total of 230 surgical procedures were included in the study. All cases were vitreoretinal surgery cases. During 37 procedures, snoring was noted, and among these, 18 patients (48.6%) moved their head suddenly. In contrast, movement occurred during only 2 of 193 procedures (1.0%) without documented snoring (P < 0.001). Thus, sudden patient head movement was approximately 49 times more prevalent in patients who snored. Continuous infusion propofol was also associated with sudden unexpected head movement (P = 0.0028). No complications as a result of the movement were identified in this study. CONCLUSION: Snoring during local anesthesia with intravenous sedation predicts a high likelihood of sudden patient movement during local anesthesia with intravenous sedation. The use of continuous infusion propofol anesthetic may increase the chance of head movement. Eye surgeons should be aware of these associations to help minimize the risk of complications caused by patient movement.

Pascal dynamic contour tonometry versus goldmann applanation tonometry in gas and air-filled eyes after vitrectomy surgery.

PURPOSE: To compare Pascal Dynamic Contour Tonometry with Goldmann Applanation Tonometry in eyes after vitrectomy surgery with intraocular tamponade of air, silicone oil or perfluorocarbon gas. METHODS: Prospective clinical comparative study. Eighty-two consecutive patients undergoing vitrectomy surgery with postoperative air, gas or oil tamponade were recruited. Intraocular pressure was measured with both devices. RESULTS: Mean Goldmann intraocular pressure was 16.6 mmHg (range, 1.0-46.0; SD = 8.80) and the mean Pascal intraocular pressure was 21.70 (range, 4.7-58.5; SD = 9.8) The mean difference between the Pascal and Goldmann readings was 5.09 mmHg (range, -14.7 to +12.9; 95% CI = 4.2-6.0; SD, 4.0; P < 0.001). Mean differences for the different tamponades were 5.09 mmHg for silicone oil, 4.02 mmHg for air, and 5.38 mmHg for perfluorocarbon gas. CONCLUSION: Pascal dynamic contour tonometry gives readings that are highly correlated with Goldmann applanation tonometry, but on average 5 mmHg higher in eyes after vitrectomy surgery with air, gas or silicone oil tamponades. The difference between Goldmann and Pascal readings does not appear to be altered by the presence of a scleral buckle, or the size of the intraocular gas bubble.

The relationship between combined positron emission tomography/computed tomography and clinical and light microscopic findings in choroidal melanoma.

BACKGROUND: To investigate the correlation between the clinical and light microscopic features of choroidal melanoma with combined PET/CT findings. METHODS: This is a retrospective interventional case series of 14 patients with choroidal melanoma referred to the vitreoretinal service at the Mayo Clinic, Rochester, MN. All underwent preoperative combined PET/CT scanning and enucleation. Standardized uptake values (SUV) were correlated with the clinical and light microscopic features of the choroidal melanomas. RESULTS: All 14 eyes showed uptake. The mean patient age was 62 years (SD 12.5 years). The mean tumor thickness was 9.3 mm (range 3-23 mm). Histopathology showed choroidal melanoma in all with the following cell types: 6 mixed cell type, 7 spindle cell type, and 1 epithelioid cell type. The average of the SUV means was 3.7 (range 1.7-12.8). The individual SUV means were correlated with lesion thickness (r = 0.85; P < 0.01) and largest tumor basal diameter (r = 0.65; P = 0.01). Melanomas with focal necrosis (P = 0.03) and of the mixed cell type (P < 0.01) appeared to have higher SUV means. CONCLUSIONS: The majority of the choroidal melanomas had low to medium mean SUVs. Lesion size accounted for a significant portion of the variation, though nonspecific necrosis and cell type were also associated with higher SUV means.

Pars planitis: a 20-year study of incidence, clinical features, and outcomes.

PURPOSE: To measure the incidence of pars planitis in a community-based population and to report clinical features, complications, and visual prognosis. DESIGN: Population-based, retrospective, 20-year cohort study. METHODS: Multicenter study using the Rochester Epidemiology Project medical records linkage system, which allows analysis of almost all patients within Olmsted County, Minnesota, with a given medical condition. Databases were searched to identify all patients with pars planitis from January 1, 1985 through December 31, 2004. Forty-six eyes of 25 patients were evaluated. RESULTS: Mean follow-up was 14.3 years. The incidence of pars planitis was 2.077 per 100,000 persons (95% confidence interval [CI], 1.43 to 2.62). The most common complications were epiretinal membrane (ERM) in 17 eyes (36%), cataract in 14 eyes (30.4%), and cystoid macular edema (CME) in 12 eyes (26.1%). Mean visual acuity after 10 years of follow-up was 20/30, with 18 of 24 patients maintaining a visual acuity of 20/40 or better. One-third of patients maintained normal visual acuity without requiring treatment. CONCLUSIONS: The visual prognosis of pars planitis is relatively good, with 75% of patients maintaining a visual acuity of 20/40 or better after 10 years. Many patients with mild disease do not require treatment. A subset of patients, however, experience severe disease with severe vision loss despite treatment. The rate of smoking and multiple sclerosis in patients with pars planitis is much higher than that of the general population.

Angioid streaks in a patient with hemochromatosis and secondary porphyria cutanea tarda.

PURPOSE: To present the clinical findings in a patient with hemochromatosis, secondary porphyria cutanea tarda and angioid-like streaks. METHODS: Retrospective clinical report. RESULTS: This patient presented with angioid like streaks and choroidal neovascularization. Hemochromatosis is a common genetic disease in the general population and presents at variable ages. The iron deposition may predispose to angioid streaks. In addition, secondary porphyria cutanea tarda (PCT) is associated with hemochromatosis and care should be taken during intraocular surgery since PCT may predispose to phototoxcity. CONCLUSION: In patients with angioid-like streaks, there should be consideration of hemochromatosis as a possible cause.

Combined positron emission tomography/computed tomography for evaluation of presumed choroidal metastases.

BACKGROUND: Choroidal metastases are the most common intraocular malignancy and are the first sign of systemic malignancy in approximately one-third of patients. Of patients with no previous diagnosis of cancer, oncological evaluation fails to find the primary lesion in approximately 50% of cases. Newer imaging modalities such as combined positron emission tomography/computed tomography (PET/CT) may improve the yield of the systemic work-up. METHODS: Consecutive patients presenting with presumed choroidal metastases were evaluated with whole body combined PET/CT scanning. RESULTS: Four patients presenting to a tertiary referral hospital with choroidal metastases as the first sign of systemic malignancy were evaluated. In all four cases, PET/CT demonstrated the ocular lesion, and the primary malignancy which was confirmed by tissue biopsy. False-negative results were seen in two cases of cerebral metastases. PET/CT demonstrated lesions not visible on CT or magnetic resonance imaging in two cases. CONCLUSIONS: Combined PET/CT is a useful addition to the work-up of patients with choroidal metastases. It provides the opportunity to detect lesions not visible with other imaging modalities and the ability to image patients with contraindications to magnetic resonance imaging. It is essential to correlate PET images with clinical information and the results of other imaging modalities and tissue biopsy remains the gold standard in the diagnosis of malignancy. False positives and negatives can occur with PET/CT, and further research is needed before this promising technology becomes a routine part of the evaluation of patients with choroidal metastases.

Treatment of nonexudative (dry) age-related macular degeneration.

PURPOSE OF REVIEW: The purpose of this report is to review the recent literature and summarize currently available and potential new treatment options for nonexudative age-related macular degeneration. RECENT FINDINGS: High-dose vitamin supplementation may have some associated systemic toxicity. It is important to check that the patient is taking beta-carotene and not vitamin A as retinal acetate or palmitate, which have been associated with osteoporosis and hepatotoxicity. High-dose vitamins E and C may be associated with cardiovascular disease. Decreasing inflammation by lowering systemic cardiac C-reactive protein, fibrinogen and cholesterol may be important, especially in light of recent epidemiologic and genetic data. The results of randomized trials of laser treatment for drusen and rheopheresis should be available during 2006. Treatment with these modalities before the results of the trials are evaluated should be avoided. SUMMARY: The holy grail of therapy for age-related macular degeneration is to avoid the development of choroidal neovascularization. High-dose vitamin supplementation should be used only in those in whom it is indicated and inflammatory parameters including highly sensitive C-reactive protein, fibrinogen and cholesterol should be stabilized because there are data associating these parameters with age-related macular degeneration and also with cardiovascular disease.

Primary treatment of choroidal amelanotic melanoma with photodynamic therapy.

The management of choroidal melanoma involves a delicate balance between preserving vision and preventing metastasis. Plaque brachytherapy has become standard management of most small lesions; however, this can result in radiation retinopathy and optic neuropathy. Transpupillary thermotherapy avoids these side-effects; however, it can also result in visual loss and its effectiveness is limited in amelanotic lesions. Photodynamic therapy with verteporfin has shown promise in animal studies of choroidal melanoma, and has recently been used in the management of lesions that have failed to respond to conventional therapy. The authors report a case of primary treatment of a small choroidal amelanotic melanoma with photodynamic therapy using verteporfin.

Amblyopia due to inflamed chalazion in a 13-month old infant.

Meibomian gland cysts (chalazia) are very common lesions in childhood and are not thought of as visually threatening lesions. A case is reported of dense amblyopia and secondary exotropia resulting from an upper eyelid chalazion.

The surgical management of consecutive exotropia.

PURPOSE: To review the results and techniques of surgical treatment of consecutive exotropia. METHODS: We performed a retrospective chart review of all patients who underwent surgery for consecutive exotropia in a pediatric ophthalmology practice between 1992 and 2001. Patients were excluded if follow-up lasted < 6 weeks or if exotropia was caused by other ocular disorders such as previous trauma or congenital cataracts. RESULTS: Fifty-nine patients were identified. The procedure performed in the majority of cases was unilateral lateral rectus recession and medial rectus advancement to the original insertion. Seven patients underwent bilateral lateral rectus recession, and 6 underwent lateral rectus recession combined with medial rectus resection. The mean interval between original surgery and surgery for consecutive exotropia was 14.1 years (range 4 months to 47.5 years). The mean preoperative distance exodeviation was 31.7 prism diopters (PD). Satisfactory alignment (ie, within 10 PD of orthophoria) was achieved in 36 patients (61%) at week 1 and 42 patients (71%) at final follow-up. Mean follow up was 16.0 months. Thirty-nine patients (66%) demonstrated an exodrift after surgery (mean 7.6 PD). CONCLUSION: Consecutive exotropia may occur many years, even decades, after esotropia surgery. Lateral rectus recession with advancement of the previously recessed medial rectus is an effective treatment. An exotropic drift occurs after consecutive exotropia surgery, usually within the first 6 weeks. A suitable ocular alignment immediately after surgery for consecutive exotropia is a small-angle esotropia of 5 to 10 PD.

Periocular keratoacanthoma: clinical features, pathology, and management.

PURPOSE: To review the clinical features and results of surgical treatment of keratoacanthoma of the eyelids. DESIGN: Retrospective, interventional case series. PARTICIPANTS: Ten patients. METHODS: Chart review of all eyelid keratoacanthomas treated between 1992 and 2001. MAIN OUTCOME MEASURES: Adequate excision, recurrence rate, and complications. RESULTS: Patient ages ranged from 27 to 78 years, with a mean age of 59 years. Six patients were male and four were female. The lesion was found on the lower lid in five patients, upper lid in two, medial canthus in two, and lateral canthus in one. The maximum diameter of the lesion varied from 2 to 25 mm, with a mean of 7.2 mm. All lesions were treated by surgical excision, with frozen-section control of margins in five cases. All lesions were excised completely with clear resection margins, and there were no cases of recurrence. The only complication was a minor wound infection in one patient. Mean follow-up was 34.5 months. CONCLUSIONS: Because of the aggressive nature and uncertain relationship to squamous cell carcinoma, we recommend excision of periocular keratoacanthoma. Surgical excision of eyelid keratoacanthoma provides good results and a very low risk of recurrence. Frozen-section control of margins should be used in selected cases to ensure complete excision.