Melih Unal

Evaluation of toxicity of intravitreal ceftazidime, vancomycin, and ganciclovir in a silicone oil-filled eye.

PURPOSE To evaluate the toxicity of intravitreal drugs in an eye filled with silicone oil for prolonged internal retinal tamponade. METHODS Vitrectomy was performed in 21 rabbit eyes, and the vitreous was replaced with silicone oil. Different concentrations of various drugs (ceftazidime, vancomycin, and ganciclovir) were injected intravitreally. RESULTS Silicone oil increased the toxicity of these drugs, which were injected in previously determined nontoxic doses, possibly because of a reduction of the preretinal space. Injecting one quarter of the known nontoxic dose failed to show any toxicity. CONCLUSIONS Nontoxic concentrations of intravitreal drugs can cause toxicity in a silicone-filled eye.

Near-Infrared and Short-Wavelength Autofluorescence Imaging in Central Serous Chorioretinopathy

Aims: The aim of the study was to compare the results of short-wavelength (SW) and near-infrared (NIR) autofluorescence (AF) in acute central serous chorioretinopathy (CSC). Methods: Twenty-six eyes of the 26 patients diagnosed with CSC (mean age 37.4 years) were included in this retrospective study. AF images were evaluated and compared with angiographic and ophthalmoscopic findings. Fluorescein angiography and AF imaging were performed using a confocal scanning laser ophthalmoscope. Results: Focally decreased AF at the leakage site was seen in most of the cases with acute CSC (20 of 26 eyes in SW-AF; 20 of 20 eyes in NIR-AF). Twenty-four of the 26 cases had decreased SW-AF corresponding to the area of the serous retinal detachment, while 19 of the available 20 cases had decreased NIR-AF corresponding to the area of the serous retinal detachment. Increased granular AF corresponding to the extent of the former retinal detachment was seen earlier with SW-AF imaging, but disappeared later in the course of disease with NIR-AF imaging. Conclusions: AF imaging in CSC demonstrates different patterns according to the course of the disease, reflecting RPE and outer retinal changes. Combining two different methods of AF imaging could predict recent or former CSC episodes and may be a non-invasive technique for monitoring CSC and performing differential diagnosis.

Problems with and pitfalls of photodynamic therapy.

OBJECTIVE To delineate the various factors that may influence the outcome of photodynamic therapy of the retina and choroid. DESIGN Experimental animal study. ANIMALS Pigmented and nonpigmented rabbits; rhesus monkeys. INTERVENTION The hydrophilic photosensitizer, mono-L-aspartyl chlorin e6, which is maximally activated at 664 nm, was studied after intravenous injection into pigmented and nonpigmented rabbits and rhesus monkeys. Laser light was supplied by a red diode laser coupled to a modified slit-lamp biomicroscope and delivered to the ocular fundus after passing through a standard fundus contact lens. Standard photodynamic parameters were used. The effects of fundus pigmentation, intraocular pressure, spot focus and defocus, region of fundus treated, equivalent fluence, and retreatment were observed in the different animal species. MAIN OUTCOME MEASURES Slit-lamp biomicroscopy, fluorescein angiography, light and transmission electron microscopy. RESULTS Fundus pigmentation appeared to be a factor only at the lowest fluence level tested, where only 4 of 12 lesions attempted in pigmented fundi were noted on fluorescein angiography, compared with 12 of 12 lesions in albino rabbits. At normal intraocular pressures and a given fluence, 10 of 10 lesions were fully manifested on fluorescein angiography, compared with 4 of 10 at 30 mmHg and 0 of 10 at pressures sufficient to blanch the optic nerve (>60 mmHg). For laser spots either focused or defocused, there were 6 of 6 lesions that were fully manifested on fluorescein angiography for each of the parameters. Lesions treated in the fovea resulted in larger spots on fluorescein angiography. The fluence of 5 mW for 10 seconds resulted in a larger lesion on angiography than the equivalent fluence of 10 mW for 5 seconds. Areas of retreatment in rabbits demonstrated more thinning of the neurosensory retina and loss of photoreceptor outer segments and nuclei than corresponding areas receiving one treatment. CONCLUSIONS Photodynamic therapy results varied, depending on intraocular pressure, region of fundus treated, ocular pigmentation, and the total time of exposure to the photosensitizer. Retreatment resulted in progressive thinning of the neurosensory retina with loss of photoreceptor outer segments and nuclei in the rabbit eye.

the Efficacy Of Plasminogen-urokinase Combination In Inducing Posterior Vitreous Detachment

Purpose: To investigate the toxicity of intravitreal plasminogen, urokinase, and their combination, and to evaluate their efficacy in the production of posterior vitreous detachment (PVD) in the rabbit eye. Methods: Fifty‐six albino New Zealand rabbits were examined before and after injection using the indirect ophthalmoscope, slit‐lamp biomicroscopy, and electroretinography. Various concentrations of urokinase or recombinant plasminogen or a combination were injected intravitreally into the right eyes of four rabbits for each concentration. The left eyes of the animals served as controls and received 0.1 mL balanced salt solution. Group 1 was injected with pure urokinase (1,000, 5,000, or 10,000 IU); Group 2 with recombinant plasminogen (0.1, 0.4, 1.0, 2.0, 4.0, 8.0, or 16.0 caseinolytic units [CU]); and Group 3 with a combination of 1,000 IU urokinase (highest nontoxic dose) and nontoxic concentrations of plasminogen (0.1, 0.4, 1.0, or 2.0 CU). The animals were killed and the eyes enucleated 15 days after injection. Electron and light microscopy were performed. Results: A concentration of 1,000 IU of urokinase was found to be nontoxic to the retina. Plasminogen concentrations of 2.0 CU or less did not produce retinal toxicity, whereas 4.0, 8.0, and 16.0 CU of plasminogen caused minimal‐to‐severe inflammatory response in the vitreous without histologic or electroretinographic changes. Neither plasminogen nor urokinase alone was successful in producing PVD. The combination of 1,000 IU of urokinase and 1.0 to 2.0 CU of plasminogen was effective without causing retinal toxicity. Conclusion: Posterior vitreous detachment can be produced in the rabbit eye using a combination of plasminogen and urokinase.

Ocular toxicity of intravitreal clarithromycin.

OBJECTIVE To investigate the ocular toxicity and clearance of intravitreal clarithromycin lactobionate (Klaricid) and to determine the highest nontoxic dose. MATERIALS AND METHODS To evaluate toxicity, 24 New Zealand white rabbits were divided into six groups (four rabbits each). Rabbits were examined preoperatively and electroretinography (ERG) was performed. The left eyes of the animals served as controls and received intravitreal injection of 0.1 mL sterile water. Klaricid (0.1 mL) was injected into the midvitreous cavity of the right eyes at concentrations of 25 microg, 250 microg, 500 microg, 1.0 mg, 2.0 mg, and 4.0 mg/0.1 mL. The animals were followed up to 15 days postinjection by clinical examination and ERG. The animals were killed and the eyes were enucleated and processed for light microscopy. Ten New Zealand rabbits were used for the vitreous clearance study as drug test rabbits and two additional rabbits were used to generate control retina and vitreous. The highest nontoxic dose (1 mg) was injected into the vitreous and the concentration of clarithromycin in the vitreous was determined using high-performance liquid chromatography at various time intervals after injection. RESULTS Cataract occurred after intravitreal doses of 2.0 and 4.0 mg. Electroretinography showed decreasing b-wave amplitude with both dark- and light-adapted stimulus in the 4.0-mg group; it was normal in other groups. Histopathologic sections showed localized retinal necrosis and disorganization with the 2.0 and 4.0 mg dosage. No histologic changes were found in the other groups. The half-life of intravitreal clarithromycin was found to be 2 hours. No metabolites of clarithromycin were observed in the vitreous samples. CONCLUSION Intravitreal clarithromycin lactobionate is nontoxic to rabbit eyes up to a dose of 1.0 mg. Because of its broad-spectrum antibiotic effect and appropriate half-life in the vitreous, it may be a good choice for intravitreal treatment of susceptible organisms.

Validation of the Ocular Trauma Score for Intraocular Foreign Bodies in Deadly Weapon-Related Open-Globe Injuries

BACKGROUND AND OBJECTIVE To evaluate the prognostic value of the Ocular Trauma Score (OTS) in cases of deadly weapon-related open-globe injuries with intraocular foreign bodies. PATIENTS AND METHODS A retrospective, interventional case series included 20 eyes of 20 patients who had deadly weapon-related open-globe injuries with intraocular foreign bodies. The OTS was calculated for each patient by adding the determined numbers of OTS variables at presentation (initial visual acuity, rupture, endophthalmitis, perforating injury, retinal detachment, and afferent pupillary defect). Patients were categorized based on their score (category 1 through 5). Final visual acuities in the OTS categories were calculated and compared to those in OTS study group. RESULTS No statistically significant difference was found between the categorical distributions of the study patients and those in the OTS study group. No patient in the study was in category 5. CONCLUSION The OTS, which was designed to predict visual outcomes of general ocular trauma, may also provide reliable information about the prognosis of deadly weapon-related open-globe injuries with intraocular foreign bodies.

Autofluorescence and OCT features of Bietti’s crystalline dystrophy

Bietti’s crystalline dystrophy (BCD) is an autosomal recessive retinal degeneration characterised by innumerable glistening intraretinal dots scattered over the fundus. This retinal degeneration was first described in three patients by Bietti in 1937 with crystalline deposits in the retina and limbal cornea.1 Progressive retinal degeneration and sclerosis of the choroidal vessels ultimately result in progressive night blindness and constriction of the visual field approximately in the third and fourth decade of life. Histopathological studies disclosed evidence of advanced panchoroidal atrophy characterised by a marked loss of the RPE and choriocapillaris and mild retinal gliosis. Focal hypertrophy, hyperplasia and intraretinal migration of RPE cells were observed.2 To the best of our knowledge, the optical coherence tomography (OCT) features of BCD have been described in a single case only.3 Herein, we report the OCT, fundus autofluorescence (FAF) and near-infrared autofluorescence (NIR AF) findings in three patients with Bietti’s crystalline retinopathy. …

Management of retinal detachment due to closed globe injury by pars plana vitrectomy with and without scleral buckling.

Background and Purpose: To investigate the effect of circumferential scleral buckling on the prognosis for patients undergoing pars plana vitrectomy and lensectomy for severe closed globe injury. Methods: A total of 33 cases in which pars plana vitrectomy and lensectomy were performed after severe closed globe injury between January 1990 and January 2003 were studied retrospectively. All patients had zone III contusion type injury according to The Ocular Trauma Classification Group criteria. Of the 33 patients, 15 (group 1) also underwent peripheral scleral buckling; 18 did not (group 2). Results: The mean age ± SD was 34.8 ± 17.5 years (range, 8–73 years). There were 6 female (18%) and 27 male (82%) patients. The two groups did not differ significantly in terms of preoperative visual acuity (P = 0.76) or postoperative visual improvement (P = 0.46). In groups 1 and 2, 4 (26%) and 3 (17%) patients developed recurrent retinal detachment for which they underwent reoperation. Other postoperative complications were as follows: group 1—phthisis (1 patient; 7%), proliferative vitreoretinopathy (1 patient; 7%), and optic atrophy (1 patient; 7%); group 2, proliferative vitreoretinopathy (2 patients; 11%) and optic atrophy (2 patients; 11%). Conclusion: Circumferential scleral buckling did not appear to offer advantages for patients undergoing pars plana vitrectomy and lensectomy for severe closed ocular injury involving the posterior chamber.

Threshold power levels for NPe6 photodynamic therapy

OBJECTIVE To determine the threshold power levels for producing retinal and choroidal vascular occlusion using mono-L-aspartyl chlorin e6 (NPe6) photodynamic therapy; to evaluate its efficacy with longer intervals between photosensitizer injection and laser application; to determine the elapsed time between light application and appearance of angiographic changes. METHODS Pigmented and nonpigmented rabbits were injected intravenously with 2 mg/kg of NPe6 before laser irradiation of the retina-choroid. Group 1 was treated at increasing power levels; fluorescein angiograms were obtained at each fluence. Group 2 animals were exposed to laser irradiation at 5 minutes, and 1 and 3 hours postinjection to determine (by fluorescein angiography 24 hours post-treatment) if increasing the interval affected outcome. Group 3 animals underwent fluorescein angiography at 30 minutes, 1 hour, 2 hours, and 24 hours posttreatment to document the time between laser application and subsequent vessel closure. RESULTS Choroidal vessel occlusion was angiographically evident in all lesions at fluences of > or = 2.65 J/cm2 in pigmented rabbits and at > or = 0.88 J/cm2 in nonpigmented rabbits. Lesion diameter decreased as the time between injection and treatment increased. Vessel occlusion was documented at least 2 hours after treatment. CONCLUSION Choroidal vessel occlusion can occur at very low fluence.

Hemicentral Retinal Artery Occlusion in a Breast Cancer Patient Using Anastrozole

Background: Anastrozole, an aromatase inhibitor, is commonly used in the adjuvant treatment of breast cancer. Anastrozole treatment is associated with a risk of thromboembolic events and retinal vascular side effects. Herein, we present a case of hemicentral retinal artery occlusion diagnosed in a breast cancer patient using anastrozole. Case Report: A 53-year-old woman with a hypertensive and diabetic background was admitted to our hospital with breast cancer. Anastrozole treatment was started after surgery, adjuvant chemotherapy, and radiotherapy. Sudden painless loss of vision in the patient’s right eye occurred within 13 months of Anastrozole treatment. A fluorescein angiogram revealed hemicentral retinal artery occlusion. Conclusion: To the best knowledge of the authors, this is the first report of hemicentral retinal artery occlusion in an anastrozole user.