Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is genetically heterogenous and approximately 35% of patients carry mutations in either of the SPG11 or SPG15 genes. Disease onset is during the first three decades of life with spastic paraplegia and mental impairment. Peripheral neuropathy and amyotrophy may occur. Kjellin syndrome is characterized by central retinal degeneration in addition to ARHSP-TCC and the disease is associated with mutations in the SPG15 gene. We identified five patients in four unrelated kindreds with spastic paraplegia and mental impairment. Magnetic resonance imaging revealed TCC, atrophy elsewhere in the brain and increased T2 signal intensity in the periventricular white matter. Probands from the four kindreds were screened for mutations in the SPG11 gene. All patients were found homozygous or compound heterozygous for truncating SPG11 mutations of which four are reported for the first time. Ophthalmological investigations revealed that the four index cases have central retinal degeneration consistent with Kjellin syndrome. PET examinations with N-[11C-methyl]-L-deuterodeprenyl (DED) and fluor-18 2-fluorodeoxyglucose (FDG) were performed in two patients with Kjellin syndrome. We observed a reduced glucose uptake in the thalami, anterior cingulum, and sensorimotor cortex indicating neuronal loss, and an increased DED binding in the thalami and pons which suggests astrogliosis. From our results we extend the SPG11 associated phenotype to comprise also Kjellin syndrome, previously found to be associated with mutations in the SPG15 gene. We anticipate that degeneration of the central retina is a common and previously unrecognized feature in SPG11 related disease.

The clinical outcome within one month after phacoemulsification cataract extraction with implantation of the blue-blocking SN60AT IOL was examined prospectively and compared to a retrospectively examined material of implantations of the equivalent SA30AL without blue-blocker. There was no difference in best corrected visual acuity gain between the two lenses. In addition, the subjective color perception was examined for with a questionnaire after the first implantation of blue-blocking IOL and after the second implantation of blue-blocking IOL. Only one patient noted a changed color perception. There are thus strong theoretical reasons to block blue light in IOLs and no short term clinical inconvenience. But, it remains to be proven in long term follow up studies that the blue-blocking IOL protects against macular degeneration.

We have developed a simulator for phacoemulsification cataract extraction. In the current project, modules for clinical evaluation were developed. The system was structured into a processing computer and an administrator interface and a trainee interface. The simulation is defined by administrator adjustable parameters and trainee adjustable parameters. The parameters may be categorized as session characteristic parameters, patient characteristic parameters and trainee characteristic parameters. The simulation is measured in variables. Further an air bubble generator was created. We believe that simulator training in future will be required for becoming cataract surgeons.

The potential of ns pulses of 266 nm from a frequency shifted NdYag laser for corneal ablation was tested on human eye bank eyes. Scanning electron microscopy demonstrated that consecutive pulses in the same spot induced thermal damage that was related to the pulse energy. The ablation threshold was estimated to 4.5 J/cm(2). The ablation per pulse slightly above threshold was 0.2-0.6 mum. It is concluded that the precision of the ablation is relevant for refractive ablations of the cornea. The higher radiant exposure required for corneal ablation at 266 nm compared to that for shorter wavelengths induces higher energy load on the cornea. To avoid heat build-up, a random flying spot is probably needed.

The transmittance of the lens capsule decreases towards shorter wavelengths from around 300 nm. There is a minimum in the transmittance of around 70% at 280 nm followed by a peak of around 75% at 250 nm and then a quick decrease to 2 - 4% at 225 nm. These results were obtained from in vitro measurement of rabbit lens capsules. It is believed that the cyclic amino acids tryptophan, tyrosine and phenylalanine are responsible for the minimum transmittance at 280 nm. It is concluded that the lens capsule efficiently protects the interior of the lens from short wave ultraviolet radiation.

The smoothness and accuracy of PMMA ablations with a prototype scanning photorefractive keratectomy (SPRK) system were evaluated by optical profilometry. A prototype frequency- quintupled Nd:YAG laser (Laser Harmonic, LaserSight, Orlando, FL) was used (wavelength: 213 nm, pulse duration: 15 ns, repetition rate: 10 Hz). The laser energy was delivered through two computer-controlled galvanometer scanners that were controlled with our own hardware and software. The system was programmed to create on a block of PMMA the ablations corresponding to the correction of 6 diopters of myopia with 60%, 70%, and 80% spot overlap. The energy was 1.25 mJ. After ablation, the topography of the samples was measured with an optical profilometer (UBM Messtechnik, Ettlingen, Germany). The ablation depth was 10 to 15 micrometer larger than expected. The surfaces created with 50% to 70% overlap exhibited large saw-tooth like variations, with a maximum peak to peak variation of approximately 20 micrometer. With 80% overlap, the rms roughness was 1.3 micrometer and the central flattening was 7 diopters. This study shows that scanning PRK can produce smooth and accurate ablations.

A prototype frequency-quintupled Nd:YAG laser was used with a scanning system to create, on poly(methylmethacrylate) (PMMA) blocks, ablations corresponding to a correction of 6 diopters of myopia by photorefractive keratectomy. The topography of the ablated samples was measured with an optical profilometer to evaluate the smoothness and accuracy of the ablations. The ablation depth was larger than expected. With a 50% to 70% spot overlap, large valleylike variations with a maximum peak-to-peak amplitude of 20 µm were observed. With an 80% spot overlap, the rms surface roughness was 1.3 µm, and the central flattening was 7 diopters. This study shows that optical profilometry can be used to determine precisely the ablation per pulse and the smoothness and accuracy of surface ablations. Knowing the exact ablation per pulse is necessary to produce a smooth and accurate corneal surface by scanning photorefractive keratectomy.

A method for calculating pulse distribution maps for scanning laser corneal surgery is presented. The accuracy, the smoothness of the corneal shape, and the duration of surgery were evaluated for corrections of myopia by using computer simulations. The accuracy and the number of pulses were computed as a function of the beam diameter, the diameter of the treatment zone, and the amount of attempted flattening. The ablation is smooth when the spot overlap is 80% or more. The accuracy does not depend on the beam diameter or on the diameter of the ablation zone when the ablation zone is larger than 5 mm. With an overlap of 80% and an ablation zone larger than 5 mm, the error is 5% of the attempted flattening, and 610 pulses are needed per Diopter of correction with a beam diameter of 1 mm. Pulse maps for the correction of astigmatism were computed and evaluated. The simulations show that with 60% overlap, a beam diameter of 1 mm, and a 5 mm treatment zone, 6 D of astigmatism can be corrected with an accuracy better than 1.8 D. This study shows that smooth and accurate ablations can be produced with a scanning spot.

The corneal-ablation rate, the beam-intensity distribution, and the initial and the desired corneal topographies are used to calculate a spatial distribution map of laser pulses. The optimal values of the parameters are determined with a computer model, for a system that produces 213-nm radiation with a Gaussian beam-intensity distribution and a peak radiant exposure of 400 mJ/cm(2). The model shows that with a beam diameter of 0.5 mm, an overlap of 80%, and a 5-mm treatment zone, the roughness is less than 6% of the central ablation depth, the refractive error after correction is less than 0.1 D for corrections of myopia of 1, 3, and 6 D and less than 0.4 D for a correction of myopia of 10 D, and the number of pulses per diopter of correction is 2500 when the beam-intensity distribution is Gaussian and 580 when it is flat.

To investigate wound healing in rabbits after corneal photoablation with a 213 nm UV scanning solid state laser. We used a frequency quintupled Nd:YAG laser to photoablate the cornea of 32 rabbits (5 mm ablation zone, 6 D myopic correction). The contralateral eyes and the eyes of 3 untreated animals served as controls. Light and electron microscopy analyses were performed on postoperative days 0, 7, 28, 90. Abnormal, light basal epithelial cells were observed during the first postoperative month, but normal epithelial maturation was evident at 3 months. Basement membrane duplication was noted. Keratocyte proliferation occurred in the anterior stroma and in a few cases, in the posterior stroma, where keratocyte activation was present. Degenerative endothelial changes were observed immediately after ablation with intracellular disorganization and junction alteration. Surface profiles with variable regularity led to a variable wound healing. Apart from differences in epithelial basal cell appearance, photoablation with a 213 nm solid state laser induced wound healing processes similar to those observed previously with prototype ArF excimer lasers. It is hoped that laser refinements will improve the surface regularity and lead to more consistent wound healing responses. However, several studies are required to assess mutagenicity, penetration depth and ablation rate of the 213 nm wavelength on ocular tissues, as well as the effects of hydration on the clinical outcome.

The optimal values of the parameters of a scanning system for laser corneal surgery are determined by using a computer model. The correction of myopia is simulated. The accuracy of the correction, the smoothness of the corneal surface after ablation, and the time needed for surgery are computed. With a beam diameter of 0.5 mm, an overlap of 60% to 80%, and a 5 mm diameter treatment zone, the simulated error is less than 0.1 Diopter for a correction of 6 Diopters or less; the roughness is less than 7% of the central ablation depth; the number of pulses per Diopter of correction is 2500 if the beam intensity distribution is Gaussian and 580 if the beam intensity distribution is uniform.