Jóhannes Kári Kristinsson

Retinal vessel dilatation and elongation precedes diabetic macular oedema

AIMS/BACKGROUND Retinal vessel dilatation is a well known phenomenon in diabetes. In this study, the theory of whether excessive changes in diameter and length of retinal vessels occur in the development of diabetic macular oedema was tested, supporting a hypothesis that the development of diabetic macular oedema may be linked to hydrostatic pressure changes described in Starling’s law. METHODS From fundus photographs of diabetic patients attending a regular eye screening programme, the diameter and segment length of retinal vessels were measured in three retinopathy groups (12 patients each) with diabetic macular oedema (DMO), background retinopathy and no retinopathy, over a period of approximately 4 years, ending at the time of diagnosis of diabetic macular oedema in the DMO group. RESULTS A statistically significant dilatation and elongation of retinal arterioles, venules, and their macular branches was found before the diagnosis of macular oedema in the DMO group. No significant changes were found in the other two groups. CONCLUSION It is suggested that Starling’s law applies to the formation of oedema in the retina as in other tissues.

Screening for eye disease in type 2 diabetes mellitus

Abstract. A screening program for diabetic eye disease was established in Iceland in 1980. Approximately 90% of the insulin dependent patients in Iceland undergo annual eye examination and fundus photography and about a fifth of the type 2 diabetic patients. We report on 245 diabetic patients with type 2 diabetes. Any diabetic retinopathy was present in 100 patients (41%), proliferative retinopathy had been present in 17 (7%) and 24 (10%) had clinically significant diabetic macular edema. Twohundred and twenty‐four patients (91%) had visual acuity equal or better than 6/12 in their better eye, 17 patients (7%) with 6/18–6/36 in their better eye, and 4 patients (1.6%) equal or worse than 6/60 in their better eye.

SYSTEMATIC SCREENING FOR DIABETIC EYE DISEASE IN INSULIN DEPENDENT DIABETES

Abstract. Under a national program established in 1980, the eyes of approximately 90% of the insulin dependent diabetic patients in Iceland have undergone annual eye examination and fundus photography. Laser treatment was given for proliferative retinopathy or diabetic macu‐lar edema according to Diabetic Retinopathy Study and Early Treatment Diabetic Retinopathy Study criteria. We report on 205 insulin‐taking patients whose age at diagnosis was less than 30 years of age. Retinopathy was present in 106 (52%) patients and proliferative retinopathy in 26 (13%). 196 patients (96%) had visual acuity equal or better than 6/12 in their better eye, 6 patients (3%) with 6/18–6/48 in their better eye, and 2 patients (1%) equal or worse than 6/60 in their better eye.

Detection of orbital implant infection with technetium 99m-labeled leukocytes.

Summary Orbital implant infection is a rare cause of anophthalmic socket pain. Because of the potential danger of infection spreading to nearby structures, it is of paramount importance to diagnose the condition as soon as possible. Scintigraphy is a method for diagnosis of graft infections by radioisotopic imaging of inflammatory sites. We report on a patient with socket pain 3 months after implantation of an acrylic implant. The socket appearance was normal and there were no signs of infection other than culture-positive socket exudation. Three consecutive computed tomography scans revealed no abnormalities. 99mTc leukocyte scintigraphy revealed white blood cell accumulation at the implantation site. The implant was removed and cultured. This produced Staphylococcus epidermidis and R. equii. A parenteral antibiotic treatment was instituted with subsequent improvement of symptoms. Four months later, after negative scintigraphy, a hydroxyapatite implant was inserted, demonstrating full vascularization on a bone scan after 2 months. Two months later, the patient developed the previous symptoms, with all of the former findings, including positive scintigraphy. The implant was removed, revealing a microabscess on the anterior aspect, producing S. epidermidis on culture. We conclude that scintigraphy using 99m Tc-labeled leukocytes is a useful technique in diagnosing low-grade orbital infection.

Formulations and toxicologic in vivo studies of aqueous cyclosporin A eye drops with cyclodextrin nanoparticles.

Cyclosporin A (CyA) is an immunosuppressive drug used topically to treat ocular inflammatory disorder such as dry eye disease (DES). It is a lipophilic cyclic peptide with molecular weight of 1202.6Da. The aim of this study was to develop surfactant free aqueous 0.2% (w/v) CyA eye drops where the drug is present in an aqueous vehicle containing CyA/cyclodextrin (CyA/CD) nanoparticles and then do three-month toxicological testing in rabbits. Five formulations of different CD concentrations were studied, all of them contained 12.5% (w/v) of α-cyclodextrin (αCD) and various amounts of γ-cyclodextrin (γCD) (ranging from 0 to 12.5% w/v). αCD was used to solubilize the drug and γCD to promote formation of complex aggregates. CyA/CD complex aggregates were formed in all the formulations tested. However, the formulation containing 12.5% (w/v) αCD and 12.5% (w/v) γCD created more CyA/CD nanoparticles of suitable size and was therefore tested in vivo. The eye drops did not cause ocular irritation or toxic side effects upon topical administration to rabbits once or twice a day for three months.

Novel CD-Based Drug Delivery System

Enhanced cyclodextrin (CD) complexation can be obtained by adding small amount of some water-soluble polymer to an aqueous complexation medium followed by heating, for example in an autoclave, to 120 to 140°C for 20 to 40 minutes. The water-soluble polymers participate directly in the complex formation, through formation of ternary complexes (or co-complexes), increasing the apparent stability constants of the drug-CD complexes. The ternary complexes possess physicochemical properties that are different from those of regular CD complexes. First, enhanced complexation increases the solubilizing properties of the CDs which reduces the total amount of CD needed to solubilize a given amount of drug. Second, each polymer molecule is able to form complexes with many drug and CD molecules. These large ternary complexes appear to be adsorbed to the surfaces of biological membranes such as to the surface of the skin or the eye, ensuring better contact between the drug molecules and the biological membranes. This results in enhanced drug delivery to the membranes and, consequently, enhanced drug bioavailability. Third, in some cases drug dissolution from solid ternary complexes is faster than from simple CD complexes. Less CD is needed in the ternary complexes and this can, at least partly, explain the faster drug dissolution observed. Finally, through polymer-CD complexation the water-soluble polymers increase the aqueous solubilities of the parent CDs without decreasing their abilities to form complexes with drugs. This will make the parent CDs, such as βCD, more attractive as pharmaceutical excipients.

2-Hydroxypropyl-ß-Cyclodextrin in Eye Drops. Evaluation of Artificial Tear-Drops In Human Patients

Relatively little is known about the effects of cyclodextrins (CDs) on the human eye, especially in patients with dry eyes. In an effort to gain more knowledge on the effects of CDs on the human eye we designed a 2-hydroxypropyl-s-cyclodextrin (HPsCD) containing eye drop preparation with cholesterol, which is a natural tear ingredient. A pilot study in rabbits and human patients was followed by an open trial and then a double masked study in patients with mild dryness. All these patients reported that they felt better in both eyes. One patient complained of crusts on the eyelid margin and this was related to the HPsCD containing artificial tears. No changes were observed in visual acuity or intraocular pressure, nor on the ocular surface or anterior eye structure.