Michael Diestelhorst

Development of a Completely Encapsulated Intraocular Pressure Sensor

A completely encapsulated intraocular pressure (IOP) sensor equipped with telemetric signal and energy transfer is introduced integrated into a silicone disc for implantation into the eye. After implantation into enucleated pig eyes and into rabbit eyes in vivo, the IOP was recorded and compared to established techniques of IOP measurement. Pressure chamber tests showed that the sensor functioned correctly after biocompatible encapsulation in polydimethylsiloxane. In vivo and in vitro tests in rabbit and pig eyes demonstrated that the implanted system worked with the same precision as established techniques for IOP determination. The correlation between the measurements with the implanted device and pneumotonometry in several experiments was between 0.9 and 0.99. This device serves as a functioning model for the realization of a telemetric IOP sensor for integration into an artificial intraocular lens. Such a device will open new perspectives, not only in the management of glaucoma, but also in basic research for mechanisms of glaucoma.

Extraocular application of mitomycin C in a rabbit model: cytotoxic effects on the ciliary body and epithelium

Since prolonged postoperative hypotony has been a frequent complication of glaucomatous filtration surgery in which mitomycin C (MMC) was used, it is important to determine the intraocular toxic effects of the drug. We placed MMC, in concentrations of 0.05, 0.2, and 1.0 mg/mL on the intact sclera of rabbits and obtained the eyes after 1, 7, and 28 days. Examination of the ciliary epithelium by transmission electron microscopy revealed an electron-dense material near the endoplasmic reticulum. Large intracellular vacuoles were present, and the mitochondria appeared swollen. These findings suggest a toxic effect of MMC on the ciliary epithelium in rabbits after extraocular application, possibly decreasing aqueous production.

Histopathology of episcleral fibrosis after trabeculectomy with and without mitomycin C

Abstract• Background: The aim of the study was to investigate the histopathologic features of scar tissue which have proliferated at the site of trabeculectomy of surgical failures after procedures with and without the use of the antimetabolite mitomycin C (MMC).• Methods: We obtained seven surgical specimens after trabeculectomy without MMC and five specimens after trabeculectomy with MMC, which were compared with 23 controls. Sections were stained with hematoxylin and eosin, Verhoeff-van Gieson, Grocott methenamine silver, and alcian blue. An immunohistochemical stain was performed for α-smooth muscle actin.• Results: Specimens from eyes operated without MMC showed dense scar tissue with many fibroblasts, much ground substance, parallel-oriented collagen fibers, and contractile intracellular proteins within the fibroblasts. Specimens from eyes operated with MMC consisted of tissue with only few fibroblasts which did not exhibit contractile proteins. Collagen fibers were arranged randomly with less ground substance.• Conclusion: Even after 1–10 months, the scar tissue was distinctly different in the two groups. These results suggest that the use of MMC has long-term effects in vivo. Surgical failures related to scar formation are possible and not reduced to zero.

Comparison of two fixed combinations of latanoprost and timolol in open-angle glaucoma

Abstract · Objective: To compare the intraocular pressure (IOP)-reducing effect of the fixed combinations of timolol 0.5% and latanoprost 0.001% or 0.005% after 4 weeks’ treatment. · Design: Following a 1-week run-in period on timolol 0.5% once daily, 139 patiens were randomized to once-daily treatment with a fixed combination of timolol 0.5% and latanoprost 0.001% (comb. 10) or latanoprost 0.005% (comp. 50) or to the individual monotherapies. The IOP was measured at inclusion and at 8 a.m., noon and 4 p.m. on days 1, 7 and 28. · Results: Comb. 10, comb. 50, latanoprost and timolol reduced IOP by 3.7, 6.1, 4.9 and 2.1 mmHg, respectively, from a baseline mean diurnal IOP (±SEM) of 24.8±0.5, 24.1±0.4, 25.2±1.2 and 24.8±0.9 mmHg, respectively. The difference in IOP reduction was significant between comb. 50 and comb. 10 (P<0.001), latanoprost (P=0.046) and timolol (P<0.001) in favor of comb. 50. There was also a significant difference between latanoprost and timolol (P=0.007), in favor of latanoprost. All treatments were generally well tolerated. · Conclusion: This study indicates that a fixed combination of latanoprost 0.005% and timolol 0.5% could be useful in the treatment of glaucoma.

Optic nerve head morphometry in healthy adults using confocal laser scanning tomography.

Background/aims: To study the optic nerve head (ONH) characteristics in a cross sectional study with confocal laser scanning tomography using the Heidelberg retina tomograph (HRT I) and thereby to obtain a new HRT database for comparison of healthy and glaucomatous eyes. Methods: White adults with no history of ocular pathology were eligible for the study. The examination comprised: assessment of visual acuity; slit lamp examination of the anterior and posterior segment; Goldmann applanation tonometry; computerised perimetry, and optic nerve head tomography with HRT. Eyes with ocular pathology were excluded. Mean (standard deviation, SD) and difference between right and left eye (RE–LE) were calculated for HRT I measurements. Differences in mean topographic parameters between male and female participants and between the age quartiles were analysed. The study included 1764 eyes of 882 healthy adults (154 females and 728 males, mean age of 46.8 (SD 8.6) years). The population investigated was larger and older in comparison with similar studies using confocal laser scanning tomography. Results: With HRT I, a mean disc area of 1.82 (SD 0.39) mm2, a mean cup area of 0.44 (SD 0.32) mm2 and a mean cup:disc area ratio of 0.22 (SD 0.13) was observed. Right eyes showed a larger mean retinal nerve fibre layer thickness (RNFLT) (0.263 (SD 0.066) mm) compared with left eyes (0.252 (SD 0.065) mm, p<0.001). Higher values in younger volunteers (mean age 35.7 years) in comparison with elderly participants (mean age 59.1 years) were noted for disc area (1.84 mm2 v 1.78 mm2) and mean RNFLT (0.263 (SD 0.06) mm v 0.249 (SD 0.07) mm) but were not significant (p>0.01). The presented results differ from published data on ONH measurements of healthy volunteers with different techniques. Conclusion: The observed differences in ONH measurements between left and right eyes seem not to be of clinical importance. This is also true for age or sex dependent changes in ONH topographies. The presented data provide a new basis for comparison of optic disc characteristics between healthy eyes and glaucomatous eyes.

Morphologic proof of the toxicity of mitomycin C on the ciliary body in relation to different application methods.

Abstract · Background: Since postoperative hypotony has been a frequent complication of glaucomatous filtration surgery with adjunctive use of mitomycin C (MMC), the question arises of whether there may be another application method which can minimize this side effect. The purpose of this study was to establish the morphologic side effects of different application methods. · Methods: MMC 0.2 mg/ml was applied to the episclera of nine eyes of six pigmental rabbits at random via collagen shield (CS), soft contact lens (CL), or lyophilisate (20 µg; LY) for 5 min. Two eyes (controls) had a subconjunctival injection of BSS only. Another control eye was left untreated (no injection). No trabeculectomy was performed. One hour later the amounts of MMC in the conjunctiva and aqueous were analyzed by reverse-phase high-pressure liquid chromatography. Ciliary bodies were dissected from the enucleated eyes, embedded and investigated by transmission electron microscopy (TEM). Cell height of the nonpigmented ciliary epithelium was morphometrically assessed by means of computer-assisted image analysis. · Results: The light-microscopic analysis of the sectioned cell area revealed reduction of the cell height of the non-pigmented ciliary epithelium (NPCE) after application with soft contact lens (foufold) and collagen shield (2.5-fold) but not with lyophilisate compared to the untreated eye. The following ultrastructural changes were seen: loss of apical microvilli (CS, CL, LY), disintegrating melanin granules within NPCE (CS), lysis of entire areas with NPCE cells (CS), myelin figures within mitochondria (LY), intracellular vacuoles (CS, CL), lysis of myelinated nerves (CS), myelin figures in mitochondria of endothelial cells (LY), and lysis of stromal fibrocytes (CS). In the control eyes (injection of BSS) none of these ultrastructural changes were detected in the cylindrical NPCE cells. The concentration of mitomycin in the aqueous humor after topical application of MMC on the episclera for 5 min were all below the detection limit (<10 ng/ml). The concentration of MMC in the conjunctiva ranged from 2.1 to 3.7 µg/g. · Conclusion: Severe morphologic alterations were seen at the electron-microscopic level after application of MMC 0.2 mg/ml with a collagen shield and with a soft contact lens. They were mildest with lyophilisate and absent in the BSS controls. A new administration device is needed if trabeculectomy is to be performed successfully using MMC in human glaucomatous eyes.

The effect of latanoprost 0.005% once daily versus 0.0015% twice daily on intraocular pressure and aqueous humour protein concentration in glaucoma patients. A randomized, double-masked comparison with timolol 0.5%

Abstract• Background: Latanoprost is a PGF2α analogue which reduces the intraocular pressure (IOP) by increasing the uveoscleral outflow. The objective of this study was to investigate the effect of two different regimens of latanoprost on the diurnal IOP and also the effect of latanoprost on the blood-aqueous barrier measured with a laser flare cell meter (Kowa FM-500). Moreover, the safety aspects of the two regimens regarding hyperemia were studied. • Methods: A double-masked, randomized study was performed in 30 patients (9 males, 21 females; mean age 61.9 years) with primary open-angle glaucoma or pseudoexfoliation glaucoma. Twenty patients were treated with latanoprost 0.0015% twice daily or 0.005% once daily for 3 weeks in a cross-over design. Ten patients received timolol 0.5% twice daily as control. • Results: Latanoprost 0.005% once daily reduced IOP (± SEM) more effectively than latanoprost 0.0015% twice daily (9.8±0.9 mm Hg and 6.7±0.9 mm Hg, respectively). There was a statistically significant increase in the aqueous humour protein concentration within the timolol group (P=0.004), but not within the latanoprost group (P=0.97). There was no statistically significant difference in the change in aqueous humour protein concentration from baseline between latanoprost and timolol groups (P=0.08). No statistically significant difference in conjunctival hyperemia between the two latanoprost regimens was found (P=0.37). • Conclusion: Latanoprost 0.005% once daily reduced IOP more effectively than latanoprost 0.0015% twice daily (P<0.001). Latanoprost had no statistically or clinically significant effect on the blood-aqueous barrier. There was no difference in hyperemia between the two regimens. Both concentrations of latanoprost reduced IOP at least as well as timolol 0.5% eye drops.

Efficacy and tolerance of diclofenac sodium 0.1%, flurbiprofen 0.03%, and indomethacin 1.0% in controlling postoperative inflammation.

Purpose: To compare the anti‐inflammatory effect of diclofenac sodium 0.1 % ophthalmic solution, flurbiprofen 0.03% ophthalmic solution, and indomethacin 1.0%. Setting: Department of Ophthalmology, University of Köln, and Bundesknappschaftskrankenhaus, Sulzbach, Germany. Methods: One hundred seventeen patients enrolled in this prospective, randomized, double‐masked, and parallel‐group study had phacoemulsification and intraocular lens implantation and received one of the three solutions. Preoperatively at day 1 and postoperatively at day 4 or 5 and day 12, 13, or 14, they were examined by slitlamp, applanation tonometry, and laser flare meter. Results: Anterior chamber flare reduction from baseline was significantly greater in the diclofenac group than in the flurbiprofen group (P = .022). Patients in the diclofenac group had significantly less burning and stinging than those in the flurbiprofen and indomethacin groups at postoperative days 4–5 and 12–14 (P = .001). Conclusion: Diclofenac sodium appeared to be more potent than flurbiprofen in controlling intraocular inflammation after cataract surgery and appeared to be locally tolerated better than flurbiprofen and indomethacin.

The efficacy and safety of unfixed and fixed combinations of latanoprost and other antiglaucoma medications.

Adjunctive therapy for the management of glaucoma is commonly used. Unfixed combinations of the prostaglandin analog latanoprost and other glaucoma medications have been demonstrated to effectively lower intraocular pressure (IOP). The range of reported additional reductions in IOP compared to a monotherapy baseline are as follows: latanoprost-timolol (13-37%), latanoprost-pilocarpine 2% (7-14%), latanoprost and carbonic anhydrase inhibitors (15-24.1%), and latanoprost and dipivefrin (15-28%). There is a fixed combination of latanoprost (0.005%) and timolol (0.5%) that has been investigated in Phase III trials in Europe and the United States. In these trials, it was noted that the efficacy of the fixed combination was superior to either of the monotherapy components. After 12 months of follow-up of patients on fixed combination, there was no evidence of long-term drift. The new formulation appears to be safe and does not demonstrate any more side effects than either of the components. The convenience of a fixed combination may enhance patient compliance. Unfixed combination therapy with latanoprost and other antiglaucoma medications and the fixed combination formulation of latanoprost and timolol provide an effective and safe option for lowering IOP in glaucoma patients.

Combined Therapy of Pilocarpine or Latanoprost with Timolol Versus Latanoprost Monotherapy

Adjunctive intraocular pressure (IOP)-lowering therapy is widely used today, as one-third of all patients being treated for glaucoma need additional therapy to reach and maintain healthy IOPs. Timolol, latanoprost, and pilocarpine are three potent drugs that have been used in combination to reduce IOP. Timolol reduces the production rate of aqueous humor to achieve the IOP decrease. Latanoprost and pilocarpine both affect aqueous outflow, although by different mechanisms. The IOP efficacy of combined therapy with timolol and pilocarpine compared with timolol and latanoprost or with latanoprost alone has been investigated in three multicenter, randomized, clinical trials in Europe. This is a review of those published trials. In 2 of the 3 studies, the additional IOP lowering effect of latanoprost 0.005% administered once daily was compared with pilocarpine 2% administered 3 times daily in patients with primary open-angle glaucoma (POAG) or ocular hypertension currently on monotherapy with timolol 0.5% twice daily. These 6-month studies found that the timolol and latanoprost combination reduced IOP more and was better tolerated with fewer side-effects than the timolol and pilocarpine combination. At 6 months, there was no evidence of long-term drift in IOP with timolol and latanoprost. This combined therapy provides an effective and safe option for lowering IOP in glaucoma patients. These results suggest that the timolol/latanoprost combination is preferable to the timolol/pilocarpine combination not only with regard to side effects but also to the magnitude of IOP reduction. Two of the 3 studies compared latanoprost monotherapy with timolol and pilocarpine combined therapy in patients with POAG, various other glaucomas, or ocular hypertension. Treatment was for 6 weeks or 6 months. In both studies, latanoprost was more effective and better tolerated than the combination of timolol and pilocarpine. These results suggest that latanoprost alone should be tried before the addition of pilocarpine to timolol therapy is considered. The convenience of daily administration of a single drop of latanoprost versus multiple drops of timolol and pilocarpine should improve patient compliance.