Purpose: To describe new disease-causing RP2 and RPGR-ORF15 mutations and their corresponding clinical phenotypes in Swedish families with X-linked retinitis pigmentosa (XLRP) and to establish genotype-phenotype correlations by studying the clinical spectrum of disease in families with a known molecular defect. Methods: Seventeen unrelated families with RP and an apparent X-linked pattern of disease inheritance were identified from the Swedish RP registry and screened for mutations in the RP2 and RPGR (for the RP3 disease) genes. These families had been previously screened for the RPGR exons 1-19, and disease-causing mutations were identified in four of them. In the remaining 13 families, we sequenced the RP2 gene and the newly discovered RPGR-ORF exon. Detailed clinical evaluations were then obtained from individuals in the three families with identified mutations. Results: Mutations in RP2 and RPGR-ORF15 were identified in three of the 13 families. Clinical evaluations of affected males and carrier females demonstrated varying degrees of retinal dysfunction and visual handicap, with early onset and severe disease in the families with mutations in the ORF15 exon of the RPGR gene. Conclusions: A total of seven mutations in the RP2 and RPGR genes have been discovered so far in Swedish XLRP families. All affected individuals express a severe form of retinal degeneration with visual handicap early in life, although the degree of retinal dysfunction varies both in hemizygous male patients and in heterozygous carrier females. Retinal disease phenotypes in patients with mutations in the RPGR-ORF15 were more severe than in patients with mutations in RP2 or other regions of the RPGR.

Purpose: To evaluate the role of particularly interesting new cysteine-histidine-rich protein (PINCH) in corneal wound healing and early neovascularization and to assess the influence of granulocytes. Methods: A standardized corneal alkali wound was inflicted under general anaesthesia to the right eye of 14 New Zealand White rabbits. Seven of the rabbits received i.v. 5 mg/kg fucoidin every 2 hours to prevent granulocytes from entering the wound area. After 36 hours, the rabbits were killed, the corneas excised, fixed in 4% formaldehyde and embedded in paraffin. The sections were double-stained with antibodies against PINCH and with haematoxylin. Results: In the normal cornea and limbus, PINCH was weakly expressed in the corneal epithelium and in a wedge of the conjunctival stroma. In the wounded corneas, PINCH expression was seen in the frontline of repopulating endothelial and epithelial cells, and in active keratocytes. The vascular endothelium and the granulocytes expressed PINCH, as did the conjunctival epithelium. In the fucoidin-treated rabbits, PINCH expression was markedly reduced. The vascular endothelial cells and the few granulocytes did not express PINCH in these rabbits. Conclusions: PINCH is only slightly expressed in the normal cornea. A corneal wound induces PINCH expression in the repopulating cells, in the vascular endothelial cells of the limbus, in the limbal epithelium and in the granulocytes. Exclusion of granulocytes reduces expression of PINCH and there is no expression at all in the vascular endothelium. © 2007 The Authors Journal compilation 2007 Acta Ophthalmol Scand.

Purpose: Relapsing polychondritis (RPC) is a rare systemic disease affecting primarily cartilaginous and proteoglycan-rich structures. It is a potentially fatal disease with unknown aetiology. There are no specific tests for RPC. The diagnosis is dependant on clinical criteria, which include chondritis of both auricles, non-erosive inflammatory polyarthritis, nasal chondritis, ocular inflammation, respiratory tract chondritis and cochlear and/or vestibular damage. Ocular symptoms will occur in approximately 60% of RPC patients. As an example, a patient with signs of RPC is described. Methods/Result: A 30-year-old woman was referred to our department for evaluation of a central corneal ulcer in the left eye. She had a history of recurrent pain in both her auricles and was also found to have a nasal septum perforation. Relapsing polychondritis was suspected. Conclusion: Non-healing corneal ulcers should alert the ophthalmologist to look for unusual reasons for this condition. RPC is one possible cause.

The retinal pigment epithelium (RPE) is of great importance in photoreceptor homeostasis. The photoreceptors are highly specialized cells which cannot survive without the RPE. It has been postulated that messenger substances are involved in the interaction between the RPE and the inner retina. In the present study, the effects on the light induced electrical responses of the eye of some possible messenger substances and their analogues were investigated. The a-, b- and c-waves of the corneal electroretinogram (ERG) and the standing potential of the eye (SP) were investigated dming simultaneous perfusion of the vitreous cavity of albino rabbit eyes with test substances alternating with a control solution. The contralateral eye of each rabbit was used as a control. To further analyze the effect on the ERG c-wave, a new in vivo method was applied. A microelectrode is advanced through the retina into the subretinal space, enabling recording of the transepithelial potential (TEP) and the slow Pili dming simultaneous perfusion of the vitreous cavity. Phenylephrine, an a.1-adrenergic receptor agonist, in a low concentration increased the c-wave and the SP, whereas clonidine, an o:.z-adrenergic receptor agonist, had similar effects on the c-wave but at higher concentration. The b-wave was also slightly elevated but there was no significant effect on the a-wave. Phenylephrine increased the TEP, while the slow Pili was reduced. These results seem to indicate that a-adrenergicreceptors are present on the apical membrane of the RPE. The effect on the b-wave and the slow Pili suggests a-adrenergic effects also on the inner retina. The stable cyclic AMP analogue, Sp-cAMPS, increased the c-wave amplitude and the SP level There was also an effect on the b-wave, but the a-wave was not affected. Both the TEP and the slow Pili were elevated. The results showed that Sp-cAMPS influences the electrophysiological properties of both the RPE and the inner retina. PhXA41, a PGF2a analogue, which is a new intraocular pressure reducing agent, did not affect the ERG and the SP at low doses. At higher doses, PhXA41 and PGF,. increased the c-wave amplitude and the SP level, while there was no effect on the a- and b-waves. The c-wave elevation was due to a reduction in slow Pili, while the TEP was not affected, indicating that receptor binding sites for PGF2• are present on the Muller cell membrane. Serotonin was shown to affect the c-wave of the ERG and the SP. The c-wave amplitude elevation was caused by an elevation of the TEP while the slow Pili was unaffected. The effects of different serotonin agonists and antagonists were also studied. The results indicate the presence of 5-HTz receptors on the RPE. There is a possibility, however, of other types of serotonin receptors being present on the RPE as well.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch's membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease.

A dysfunction of the retinal pigment epithelium (RPE) is the main cause for the development of age-related macular degeneration (ARMD) and visual loss in elderly people. For about 10 years experimental and clinical attempts to transplant RPE cells have been performed. The aims of this study were to elucidate the long term results of RPE allografts, to develop an atraumatic transplantation technique, and to explore the cellular response to RPE allografts, melanin granules, and autologous IPE cells.

Surgery was performed on rabbits with a follow-up period of up to six months. After a pars plan vitrectomy, a subretinal bleb was created into which a suspension of RPE/IPE donor cells or melanin granules was injected. Pigmented RPE donor cells or preparations of melanin granules were implanted subretinally in albino rabbits. Pigmented rabbits were used in IPE transplantation. The eyes were monitored with ophthalmoscopy, fundus photography, light microscopy, electron microscopy and immunohistochemistry.

Transplantation of suspensions of fresh pigmented RPE cells to the subretinal space in rabbits is feasible and induces virtually no complications when an atraumatic surgical procedure is used. The allograft forms a monolayer in conjunction with the native RPE and persists almost intact up to three months. At six months after transplantation, there was a cellular response exhibiting multilayers of cells, such as RPE and macrophages. Damage to adjacent photoreceptors in combination with melanin granules in the subretinal space indicates graft failure. No infiltration of lymphocytes was seen. Whether the cellular response was due to immunological or non-immunological mechanisms could not be determined from this experiment.

Cyclosporine (CsA) could not prevent disintegration of the RPE transplant and graft failure. CsA was not capable of promoting graft survival as compared to the controls. The transplant seems to be disrupted either by immunological mechanisms that are not inhibited by CsA, or by non-immunologic events.

Implantation of melanin granules to the subretinal space of albino rabbits induces a considerable phagocytic cellular response involving the host’s RPE, macrophages and glial cells. The migration of pigment-laden cells into the neural retina was frequently associated with focal photoreceptor damage. The cellular response was identical to that ensuing RPE cell transplantation. These findings support the concept that non-immunological events have a considerable influence on the outcome.

In order to evaluate the impact of non-immunological mechanisms, a technique of transplanting fresh autologous IPE cells to the subretinal space of the same eye was developed. Grafted IPE cells were seen to survive for six months. There was a remodeling of the compound cellular layers in the subretinal space over time where grafted IPE cells joined the native RPE cells. The cellular response that developed exhibited macrophages, but no lymphocytes, and was in this respect similar to that observed following RPE transplantation.

In RPE allografts, the photoreceptors appeared normal on light microscopy at three months, but at six months, the photoreceptors overlying the transplants generally exhibited pathological changes. In autologous IPE grafts, on the other hand, the photoreceptors displayed normal outer segment length and outer nuclear layer on top of grafted IPE cells. Focally, multilayers of both grafted IPE and RPE cells, together with macrophages, induce damage to adjacent photoreceptors as observed at 6 months. Cellular multilayers in the subretinal space, irrespective of genesis, are likely to have adverse effects on photoreceptors. The experiments using autologous IPE grafts show that non-immunogenic mechanisms have a decisive impact on the outcome of the transplant in the subretinal space.

Purpose: To determine the effects of systemic cyclosporine A (CsA) on the survival of retinal pigment epithelial (RPE) allografts in the subretinal space in an animal model using atraumatic transplantation surgery.

Methods: Following pars plana vitrectomy, an RPE cell suspension from brown rabbits was injected with a glass micropipette into the subretinal space of 39 albino rabbits. For immunosuppression, 22 rabbits were given an injection of CsA, 20 mg daily intramuscularly, 17 rabbits with RPE grafts were controls. The grafts were monitored by biomicroscopy, color fundus photography, and fluorescein angiography. Rabbits were sacrificed at 1, 3 and 6 months, respectively, and the eyes processed for light and electron microscopy including immunohistochemistry.

Results: After three months, the transplanted RPE cells, in both the CsA group and the controls, formed a monolayer in the subretinal space. Although a few macrophages were encountered, there was no massive cellular infiltration and the photoreceptor layer was well preserved. After six months, however, there was a disruption of grafted RPE cells in both groups, characterized by dispersion of melanin pigment in the subretinal space, and invasion of macrophages with focal photoreceptor damage but no infiltration of lymphocytes in the retina or choroid. No significant differences between the CsA treated and the control eyes were discernible.

Conclusion: Although the subretinal space has been considered an immunologically privileged site, we found that the survival of RPE allografts was limited. CsA did not prevent RPE allograft destruction in the subretinal space. The transplant seems to be disrupted either by immunological mechanisms that are not inhibited by CsA, or by nonimmunologic events.

Purpose: To determine the long-term RPE allograft survival in the subretinal space using suspensions of RPE cells and atraurnatic transplantation surgery.

Methods: Nineteen albino rabbits were transplanted with suspensions of pigmented RPE cells from brown rabbits. Following pars plana vitrectomy, the RPE cell suspension was injected through a small retinotomy using a glass micropipette into the subretinal space under microscopic control. No immunosuppression was used. The eyes were monitored by biomicroscopy, color fundus photography, and fluorescein angiography. Rabbits were sacrificed at 1, 3 and 6 months, respectively, and the eyes processed for light and electron microscopy, using monoclonal antibodies for identifying macrophages.

Results: Transplanted RPE cells were present in the subretinal space in all eyes at 6 months. There was no fluorescein leakage. Generally, the RPE allograft formed a monolayer, but focal fragmentation and disruption with dispersion of melanin pigment occurred. Foci of multilayers of cells in the subretinal space, containing large macrophages, were associated with adjacent photoreceptor damage. There was no infiltration of lymphocytes but macrophages and glial cells were contiguous to the transplant. Cells harboring intracytoplasmatic melanin pigment were observed in the neural retina.

Conclusion: Transplantation of RPE cell suspensions to the subretinal space generally forms a monolayer that persists at 6 months, However, in areas of multilayers of RPE cells and macrophages, graft failure occurs in combination with adjacent photoreceptor damage. Graft failure is not associated with the infiltration of lymphocytes, but other mechanisms seem to occur.

Background: In some retinal diseases and following transplantation of retinal pigment epithelium (RPE), melanin granules are liberated to the subretinal space. Our aim was to investigate the cellular response to implanted extracellular melanin.

Methods: After pars plana vitrectomy, 17 albino rabbits received a suspension of melanin granules in the subretinal space. Postoperative examination included ophthalmoscopy, color fundus photography, histology using monoclonal antibodies identifying RPE cells (AE1/3), macrophages (RAM 11), B-lymphocytes (CD20) and T-lymphocytes (CD45), and electron microscopy. The follow-up time was 2 weeks, 4 weeks and 6 months.

Results: On fundus photographs, the layer of melanin showed focal attenuation with lighter areas at 6 months. Melanin granules were phagocytosed by RPE cells and macrophages at 2 weeks, as identified by monoclonal antibodies. In areas where an abundance of melanin was present, multilayers of macrophages were seen associated with considerable photoreceptor damage. Pigment-laden cells invaded the neural retina. The cellular infiltration of the retina was focal, and when it involved the outer nuclear layer the photoreceptor damage was severe. Electron microscopy demonstrated the presence of melanosomes intracellularly in Müller glia. The process of phagocytosis and removal of melanin granules from the subretinal space was slow and not completed at 6 months.

Conclusion: Our experiments show that implantation of melanin granules in the subretinal space of albino rabbits may induce a considerable phagocytic cellular response featuring the host’s RPE, macrophages and glial cells. The migration of pigment-laden cells into the neural retina was associated with focal photoreceptor damage.

Purpose: To study the effects of transplanted iris pigment epithelial (IPE) cells in the subretinal space on the survival of adjacent photoreceptors.

Methods: An upper iridectomy was made on the right eye of 37 pigmented rabbits. Suspensions of autologous IPE cells were prepared and injected into the subretinal space of the same eye. Follow- up examinations was performed using ophthalmoscopy and calor fundus photography. At 1, 2, 3 and 6 months, respectively, the rabbits were sacrificed and the eyes examined with light and electron microscopy.

Results: On histological examination, the photoreceptor cells were well preserved in grafted areas at 1-3 months. At 6 months, also, the photoreceptors generally disclosed a normal nuclear layer and long outer segments when overlying areas with single cells or clusters of IPE. However, multilayers of transplanted I PE, native RPE cells and macrophages in the subretinal space were frequently associated with photoreceptor damage and nuclear drop out from the outer retinal layer.

Conclusion: In this experimental model, the photoreceptors generally survive adjacent to grafted IPE cells for 6 months. Multilayers of subretinal cells are likely to induce adverse effects on adjacent photoreceptors which is a new finding that requires further investigation.

Purpose: To investigate the cellular morphology in the subretinal space following transplantation of iris pigment epithelial (IPE) cells from the same eye. Methods: Following an iridectomy, fresh IPE cells were prepared and no culturing performed. After pars plana vitrectomy, a suspension of autologous IPE cells was injected into the subretinal space in 37 rabbits. The grafts were monitored by ophthalmoscopy and colour fundus photography. Rabbits were sacrificed at 1, 2, 3 and 6 months, respectively, and the eyes examined with light and electron microscopy. Results: The grafted area retained the same configuration over 6 months but then appeared less pigmented. At 1-3 months, the IPE formed one or more contiguous layers on top of native RPE. At 6 months, cells compatible with grafted IPE were present in the subretinal space, often forming monolayer-like chains integrating with the native RPE. Depigmented cells of presumed IPE origin were seen and frequently in association with abundant melanin granules located in the apical portion of adjacent RPE cells. In such areas, large macrophage-like cells were observed. Conclusion: Transplanted IPE cells survived for up to 6 months in the subretinal space. Our observations suggest a scenario of remodelling of the cellular layers in the subretinal space over time where grafted IPE cells formed a compound layer with the native RPE. Transplantation of autologous IPE cells may have a potential as a treatment modality in selected cases of age-related macular degeneration.

Purpose: To investigate photoreceptor survival in transplantation of non-cultured iris pigment epithelial (IPE) cells to the subretinal space in a prospective experimental study. Methods: Upper iridectomies were carried out in the right eyes of 37 pigmented rabbits. Suspensions of freshly harvested autologous IPE cells (without culturing) were prepared and injected into the subretinal space of the same eye. Follow-up examinations were carried out using ophthalmoscopy and colour fundus photography. The rabbits were killed at 1, 2, 3 and 6 months, respectively, and the eyes examined with light and electron microscopy. Results: On histological examination, the photoreceptor cells were found to be well-preserved in grafted areas at 1-3 months. At 6 months, the photoreceptors generally disclosed a normal nuclear layer and long outer segments when overlying areas with single cells or clusters of transplanted IPE cells. Multilayers of cells in abundance, including native RPE cells and macrophages (stained with RAM 11), particularly under microfolds of the neural retina, were occasionally associated with photoreceptor damage and nuclear drop out from the outer retinal layer. There was no inflammatory response in the choroid and the choriocapillaris remained patent. Conclusion: The experiments show that grafting freshly harvested autologous IPE cells to the subretinal space is feasible and that the photoreceptors generally survive for at least 6 months when overlying the transplanted areas. Multi-layers of abundant cells in the subretinal space may induce adverse focal effects on adjacent photoreceptors.

Purpose: To investigate the cellular morphology in the subretinal space following transplantation of iris pigment epithelial (IPE) cells from the same eye.

Methods: Following an iridectomy, fresh IPE cells were prepared. After pars plana vitrectomy, a suspension of autologous IPE cells was injected into the subretinal space in 37 rabbits. The grafts were monitored by ophthalmoscopy and calor fundus photography. Rabbits were sacrificed at 1, 2, 3 and 6 months, respectively, and the eyes examined with light and electron microscopy.

Results: The grafted area retained the same configuration over 6 months but then appeared less pigmented. At 1-3 months, the IPE formed one or more contiguous layers on top of native RPE. At 6 months, cells compatible with grafted IPE were present in the subretinal space forming mono-layer like chains integrating with the native RPE. Depigmented cells of presumed IPE origin were seen. lt was commonly observed that the apical portion of RPE cells disclosed abundant melanin granules. With time the grafted cells appeared to decrease in number but focal clusters of IPE cells and large macrophages were present.

Conclusion: Transplanted IPE cells survived for up to 6 months in the subretinal space. Our observations suggest a scenario of remodeling of the cellular layers in the subretinal space over time where grafted IPE cells formed a compound layer with the native RPE. Transplantation of autologous IPE cells may have a potential as a treatment modality in selected cases of age-related macular degeneration with impending degeneration of RPE and choriocapillaris.

Background: Phototherapeutic keratectomy (PTK) has been employed as a surgical tool to treat corneal disease for more than 10 years. The laser has made it possible to remove superficial corneal opacities and thereby restore vision. The 193 nm ultraviolet light separates molecules and splits molecules in biological tissue, thereby ablating it. About 0.25 ╡m of tissue is ablated by each pulse. The development of the excimer laser technique has been fast. It has principally focused on refractive surgery but has also benefited PTK. Corneal dystrophies: The ability to delay or postpone corneal grafting in superficial corneal dystrophies represents a very important achievement. Map-dot-fingerprint dystrophy or basal membrane dystrophy is a common indication for PTK. Other dystrophies such as Meesman's, Reis-Bⁿckler's, Thiel-Benke's, granular, macular, lattice and Schnyder's can be treated, although with differing degrees of success and varying rates of recurrence. Subepithelial scarring in Fuchs' dystrophy has been ablated. Other trials have involved the removal of substantial parts of the stroma in order to reduce the load on the endothelium. Recurrent dystrophic changes can likewise be removed from corneal grafts and thus prevent the need for regrafting. Recurrent erosions: Laser treatment has made it possible to manage wound-healing problems better after recurrent erosions. Recurrent erosions are the most common indications for PTK: several studies show good and persistent effects with this type of treatment. Persistent epithetial defects of various origins, among them corneal ulcers resulting from allergic disease, can likewise be treated. Scar tissue: Scars after surgery such as pterygeum excision can be removed. Smooth muscle actin containing fibroblasts in old scars should be given special consideration in PTK. Excimer laser surgery can be successfully combined with conventional surgery to remove excessive scar tissue, Salzmann's nodules and very flaky and coarse band keratopathy. Irregular corneal surfaces following ulcers and injuries pose problems that have so far proved difficult to overcome. Thinning is often seen after bacterial corneal ulcers or after herpes simplex keratitis. A rough or uneven surface can be made smoother by using modulators during treatment by casting a new surface under a hard contact lens (PALM technique), a surface that is then projected into the stroma by laser ablation. Modern techniques linking the excimer laser with computerized corneal topography and wavefront analysis promise to further improve the smoothing capacities of lasers and to increase the quality of optical results. Complications: The most feared complication of PTK is the postoperative infection. These are rare. Haze is usually not prominent but scar tissue formation of a more persistent type has been noted after laser surgery in eyes with pre-existing surgical scars. Keratectasia has been described after PTK. Failure due to deep opacities or a surface that is too uneven is a more common frustration. This paper reviews advances in excimer laser treatment of corneal disease.

Purpose: To describe corneal opacities of a new type and distribution in a small family. Methods: Family members were interviewed and examined to establish a pedigree and to detect any corneal abnormalities. Results: Two family members presented with corneal opacities. Both had, in the very peripheral cornea, flat, greyish, rounded opacities, 20-200μm in diameter, on the Descemet's membrane. In addition, the mother had the same type of opacities over the central cornea just inside the Bowman's layer. The remaining parts of the corneas were clear. Vision was unaffected and the opacities caused no discomfort. There was no other corneal pathology. The subjects' general health was good. Conclusions: To our knowledge, these types and distribution of corneal opacities have not been described previously. Although the mode of inheritance at this point is uncertain, we believe the changes are of a dystrophic nature. © 2007 Acta Ophthalmol Scand.

Purpose: To study the change in expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 in the rabbit cornea and limbus following a penetrating, central corneal alkali burn. The influence of different cells on VEGF and VEGFR-2 expression was studied by excluding granulocytes from the wound area. Methods: Fourteen New Zealand white rabbits were subjected to a penetrating, 5-mm diameter, central corneal alkali burn in one eye under general anaesthesia. Seven of the rabbits were given injections of fucoidin for 36 hours. The rabbits were killed after 36 hours and the corneas were excised with a sclera rim and prepared for immunohistochemistry. Results: Both VEGF and VEGFR-2 are strongly expressed in the frontline of repopulating epithetial, stromal and endothelial cells during wound healing, irrespective of granulocyte presence. Vascular endothelial cells express VEGF strongly after injury, but only in the presence of granulocytes. Conclusion: Corneal neovascularization requires the presence of granulocytes to stimulate vascular endothelial cells. During wound healing in this area, VEGF is a factor that stimulates proliferation and migration and that is not influenced by granulocytes.

Purpose: To evaluate the effect of phototherapeutic keratectomy (PTK) in combination with manual scraping when removing epithelial ingrowth under a LASIK flap.

Material and Methods: Three patients, who had undergone several surgeries following LASIK in order to remove epithelial ingrowth that was threatening vision, were treated with a flap lift, manual abrasion and PTK. The PTK was performed on both the stromal and the flap side with the aim of eliminating the threat and improving vision. Two patients underwent primary surgery to remove epithelial ingrowth with manual abrasion and PTK. The influence on vision, topography and cell recurrences was evaluated.

Results: Uncorrected visual acuity (UCVA) and best spectacle-corrected visual acuity (BSCVA) improved in four cases and remained good in the fifth case. The refraction did not change significantly. Topography disclosed changes in the irregular astigmatism, explaining the improved BSCVA. Central epithelial ingrowth did not recur, whereas peripheral ingrowth did. The peripheral ingrowth did not progress, except in case 1, where a cyst formed that required surgery.

Conclusions: It is our belief that adding PTK to manual scraping improves the prognosis for eyes with epithelial ingrowth. It is mainly the central ingrowth that is positively affected. Improved adhesion between the stroma and the flap is one possible explanation.

Age-related maculopathy (ARM) may progress into age-related macular degeneration (AMD), which is often disastrous to near vision and reading. Currently used treatment is generally not successful in a long-term perspective. Therefore, searching for an early detection of functional disturbances as well as for prophylactic treatment appears important.

Colour contrast sensitivity was measured in patients with soft drusen maculopathy (early ARM). No deterioration in visual function was observed with conventional tests. A highly significant elevation (p<0.001-0.0001) of thresholds for all three colour axes was found, indicating an impairment of retinal function. A tendency towards a bimodal distribution was seen, suggesting a subgroup with a more prominent decrease in foveal sensitivity and possibly at higher risk of progression into the exudative form of the disease. Colour contrast sensitivity appears to be a more sensitive measure of early functional disturbances of the retina than provided by the currently used tests.

Contrast sensitivity was measured peripheral to an absolute central scotoma in patients with AMD and was found to be significantly lower (p<0.001) than In normals at the same degree of eccentricity. This finding may explain the variations in the need for magnification in low vision patients with identical visual acuity for achieving the same visual performance.

A new system for evaluating paramacular function and establishing the most suitable area for eccentric viewing was designed. The method facilitates the procedure of teaching and training the patient to use the eccentric viewing technique successfully. Reading speed increased significantly (p<O.OOl) with significantly fewer one-hour training sessions (p<O.OOl) than needed with the current training method.

In a prospective, randomised study, patients with early ARM were treated with green argon laser photocoagulation perifoveally over the drusen area. Parameters such as visual acuity, colour contrast sensitivity and central visual field were unchanged at the 12-month follow-up. The total drusen area decreased significantly (p<0.0001) after laser photocoagulation over a period of 12 mOnths. No complications were noticed. In a matched control group, the area of drusen tended to increase, and there was a significant difference {p<O.OOl) in drusen area between the two groups after 12 months. In the control group, mean visual acuity (p=0.008) and colour contrast sensitivity along the tritan axis {p=0.044) decreased, and three patients advanced to the exudative stage of AMD during follow-up. The results seem to indicate a promising prophylactic potential of the treatment.

Purpose: To investigate the effects of photodynamic therapy (PDT) on juxtafoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD) in a clinical patient material. Methods: Thirty eyes in 30 consecutive patients with AMD and a juxtafoveal CNV underwent PDT with verteporfin with standard parameters. The patients were followed up for 12 months and retreated every 12 weeks in the event of leakage from CNV. Nineteen patients (63.3%) had a predominantly classic CNV, eight (26.7%) had a 100% occult CNV and three (10%) had a minimally classic lesion. In 27 patients (90%) the lesion was ≤ 3 MPS (Macular Photocoagulation Study) disc diameters and ≤ 3 MPS disc areas. Results: There was a positive correlation between duration of symptoms and loss of visual acuity at 12 months (p < 0.02). For predominantly classic lesions, there was a positive correlation between duration of symptoms and lesion size (p < 0.005). At 12 months, leakage had stopped after 3.3 ± 0.9 treatments in 80% of the patients. Visual acuity remained stable in 63.3% of the patients. Conclusion: Photodynamic therapy appears to be beneficial in patients with AMD and juxtafoveal CNV. Copyright © Acta Ophthalmol Scand 2004.

Purpose: To study the effect of mild laser treatment on the incidence of exudative complications in patients with soft drusen maculopathy in a longterm perspective. Methods: In a prospective study, 38 patients with early age-related maculopathy and good visual acuity (VA) were randomized either to laser treatment using an argon green laser or to observation. At 8 years, 29 patients remained in the study, 16 in the control group and 13 in the treatment group. Results: During follow-up, mean VA decreased significantly in both groups, to 0.53 in the treatment group (p < 0.05) and to 0.25 in the control group (p < 0.001). At 8 years, 9/16 in the control group showed exudative complications, whereas only 2/13 in the treatment group developed such changes (p < 0.03). Conclusion: In this randomized pilot study, mild laser treatment of soft drusen maculopathy significantly reduced the rate of exudative complications in a longterm perspective. As the study is small, the results should be viewed with caution.

Purpose: To investigate the effects of photodynamic therapy (PDT) on subfoveal choroidal neovascularization (CNV) in age-related macular degeneration (AMD) in a Swedish patient material with smaller lesions than those investigated in the TAP (Treatment of Age-related Macular Degeneration with Photodynamic Therapy) and VIP (Verteporfin in Photodynamic Therapy) Studies. Methods: Photodynamic therapy with verteporfin was performed according to the results and recommendations of the TAP and VIP Studies. The patients were followed up for 12 months and retreatment was performed every 12 weeks when leakage from CNV was present. Of the 100 eyes in the first 100 patients with a follow-up period of 12 months, 59% had a predominantly classic lesion, 36% had an occult-only lesion and 5% had a minimally classic lesion. The greatest linear dimension (GLD) was ≤3 NIPS (Macular Photocoagulation Study) disc diameters (DD) in 73%, 39% and 20% of lesions, respectively, for the three groups. The actual lesion area was ≤3 MPS disc areas (DA) in 85%, 50% and 40% of lesions, respectively. There was a positive correlation (p < 0.05) between the duration of symptoms and GLD, as well as between the duration of symptoms and the lesion area (p < 0.02). Results: At 12 months, visual acuity had remained stable or increased by ≥3 lines (ETDRS) in 61% of patients with predominantly classic lesions, in 61% of patients with occult-only lesions and in 60% of patients with minimally classic lesions. Leakage had stopped after 2.9 ± 0.9 treatments in 77% of the total group of patients. Conclusion: The visual outcome was comparable to those of the TAP and VIP Studies (p > 0.3). Regarding the effect on leakage, however, our results are far better than those of the TAP and VIP Studies. The proportion of patients in which leakage had stopped was almost three times that of the TAP (27%) and VIP (26%) Studies. It seems likely that this difference was caused by the fact that the lesions in our study were much smaller, on average, than those in the TAP and VIP Studies.

Glaucoma is one of the most common causes of blindness in the world, and it is important that screening tests as well as treatment possibilities are improved continuously. A reliable but more rapid screening test than those already available would be of great interest. In addition, new and more effective treatment options would be most valuable. The aims of the present thesis were to evaluate the reliability of a new and rapid peripheral colour contrast sensitivity test as a tool for glaucoma screening and to gain more information on latanoprost, a recently developed prostaglandin analogue, in glaucoma treatment.

Colour contrast sensitivity was analysed with a system described by Arden and co-workers, using a computer controlled colour monitor. The test objects for the central test were letters of standard optotype subtending a visual angle of 3° . For the peripheral test, the test object was a colour contrasting annulus concentric with a fixation spot. The annulus had a radius of 12.5° in the extramacular field and a width of 1°. The colour contrast of the letter or the annulus in relation to the background could be changed, and a colour contrast threshold value could be obtained in the protan, deutan and tritan colour axes.

In a study of glaucoma patients, ocular hypertensive patients and normals, the peripheral colour contrast sensitivity test was found to distinguish the glaucoma patients from the normals. However, it was difficult to find a reliable cut-off point if the test is to be used as a screening test.

In a five-year prospective study of ocular hypertensive patients, the peripheral colour contrast sensitivity test could not clearly predict which patients would develop glaucoma and which would not, given that the Glaucoma Herrrifield Test is used as the golden standard. A change over time in the protan axis may, however, indicate glaucoma development. For a test to be used in glaucoma screening, it is necessary to know whether other common eye diseases such as diabetes and cataract affect the outcome. Therefore, the influence of diabetes and cataract on peripheral and central colour contrast sensitivity was also studied.

Diabetes type II was found to affect both peripheral and central colour contrast sensitivity, the tritan axis being the most affected one. For the tritan axis, the central colour contrast sensitivity seemed to correlate well with the degree of diabetic retinopathy, indicating the possibility of a new functional test of diabetic retinopathy.

Cataract, even moderately developed, affected both peripheral and central colour contrast sensitivity. Central colour contrast sensitivity seemed to be poorer in pseudophakic eyes than in normal eyes. Thus, both diabetes type II and moderate to severe cataract must be considered if the colour contrast sensitivity test is to be used for glaucoma screening. The choice of material for the IOL may also be of importance for postoperative central colour contrast sensitivity.

The prostaglandin analogue latanoprost effectively reduces the IOP at the original concentration of 0.005%. However, several patients need additional treatment. Therefore, the effect of pilocarpine in combination with latanoprost was studied. When pilocarpine was added to latanoprost, there was an additional reduction in the intraocular presure (IOP) (7.4%), and when latanoprost was added to pilocarpine the reduction was even more pronounced (142%). Therefore, it seems that latanoprost and pilocarpine can be combined in glaucoma treatment.

In certain eyes, an increased iris pigmentation was seen as a side-effect of latanoprost. This side-effect may be dose-dependent. Therefore, the original concentration of 0.005% was compared to a lower concentration, 0.001%. Latanoprost 0.005% was more effective than latanoprost 0.001% in reducing the IOP. However, the lower concentration was sufficiently effective to have a potential for clinical use in many patients. Latanoprost 0.005% gave an lOP reduction of 35% after four weeks of treatment, which was in agreement with earlier results. The lower concentration was, however, surprisingly effective and gave an IOP reduction of 27.7%.

Purpose:  To evaluate a peripheral colour contrast sensitivity test as a tool for early diagnosis of glaucoma in a five-year prospective study.

Patients and methods: Peripheral colour contrast sensitivity was measured with a computer graphics system developed by Arden et al. The test colours were varied along the protan, deutan and tritan colour confusion axes on a scale from 0 to 100 percentage units. Fifty-five ocular hypertensive (OH) patients examined with the colour contrast test, stereoscopic photography of the optic discs, and measurements of visual fields (Humphrey 24–2 glaucoma hemifield test (GHT)) in 1994, were re-examined after five years.

Results:  Ten patients were ‘outside normal limits’ in the GHT at follow-up. This group of 10 patients did not differ in colour contrast thresholds at the test in 1994 from the 45 who were still ‘normal’ (or ‘borderline’) at follow-up. Neither were there proportionally more patients with GHT ‘outside normal values’ for the patients with high colour contrast thresholds (> 30% units) in 1994 regarding any of the three colour axes. As judged from patient files, 27 patients had developed glaucoma during follow-up. Although there were differences between these 27 glaucoma patients and the remaining OH group at the colour contrast test in 1994, these differences did not reach statistical significance for any of the colour axes (largest difference in the tritan axis: 6.2% units, P = 0.0745). At follow-up, however, there was a significant difference in colour contrast for the protan axis between the clinical glaucoma group and the OH group (6.7% units, P = 0.0105).

Conclusion: The method used for colour contrast measurement did not reveal glaucomatous changes before conventional perimetry (Humphrey 24–2, GHT). Neither did it predict the patients who, in our clinic, subsequently developed glaucoma during a five-year period. A change over time in colour contrast in the protan axis for an OH patient may, however, indicate glaucoma development.

Purpose: To study the influence of diabetes, with or without early retinopathy, on peripheral and central colour contrast sensitivity.

Methods: The study included 32 patients with diabetes mellitus type II and 47 age-matched normals. The patients were divided into three sub-groups. 1. Diabetics with no retinopathy (on photographs or biomicroscopy). 2. Diabetics with microaneurysms only. 3. Diabetics with microaneurysms and hard exudates. Colour contrast sensitivity was measured with a computer graphics system along the protan, deutan and tritan axes.

Results: The peripheral colour contrast thresholds were significantly elevated for all axes when comparing the group with microaneurysms and exudates to normals. There were also significant differences between the group with microaneurysms and hard exudates and the two other diabetic groups, respectively, but only for the tritan axis. Diabetics with no retinopathy or with microaneurysms only did not differ significantly from normals.

The central colour contrast thresholds showed significant differences between normals and the group with microaneurysms, but only for the protan and deutan axes. There were significant differences for all three axes between normals and the group with microaneurysms and hard exudates. There were also significant differences between the group with microaneurysms and hard exudates and the two other diabetic groups, but only for the tritan axis. Diabetics with no retinopathy did not differ significantly from normals.

Conclusion: Peripheral colour contrast sensitivity was affected by low-grade diabetes type II retinopathy. This finding has to be considered if the method is to be used in screening for glaucoma. The central colour contrast sensitivity test seems to correlate to the degree of retinopathy and thereby perhaps provides a new screening method for diabetes retinopathy. Further studies are required in order to evaluate such a possibility.

Purpose: To evaluate a new test for peripheral colour contrast sensitivity as a tool for early diagnosis of glaucoma.

Patients and Methods: Peripheral colour contrast sensitivity was measured by a computer and colour monitor system developed by Arden and co-workers. The monitor displays an annulus subtending 25° at the retina. During the test, 45° of the annulus is removed in one of four quadrants. The patient is asked to identify this quadrant, first at suprathreshold levels and then as the colour contrast between the annulus and the background is varied in order to establish the threshold for identification. The tested colours were varied along the protan, deutan and tritan colour confusion axes, respectively. Thirty-three normal subjects, 22 glaucoma patients and 69 ocular hypertensive patients were examined. The ocular hypertensive patients were divided into a low risk group, a medium risk group and a high risk group.

Results: The colour contrast thresholds for the glaucoma group and the high risk ocular hypertensive group were significantly (p<0.001) higher for all three colour axes compared with the normal group. There were also significant (p < 0.05-0.001) differences for all axes between the glaucoma group on the one hand and the ocular hypertensive low risk group on the other hand. There were, however, overlaps in colour contrast thresholds between all groups.

Conclusion: Although there is a large and statistically significant difference in average colour contrast thresholds between normals and glaucoma patients, it was difficult to find an appropriate cut-off point to separate the two groups. Further studies must clarify the influence of early stages of common diseases such as cataract, diabetes and age-related maculopathy on colour contrast sensitivity.

Purpose: To study the influence of cataract on peripheral and central colour contrast sensitivity.

Methods: Peripheral and central colour contrast sensitivity was measured with a computer graphics system along the protan, deutan and tritan axes. Included were 30 patients with cataract divided into three sub-groups: cortical cataract, nuclear sclerosis and posterior subcapsular cataract. Colour contrast was measured before and after cataract operation.

Results: There were significant differences in peripheral colour contrast thresholds comparing the preoperative and postoperative results. This difference existed even in patients (n=19) with a pre-operative visual acuity ≥0.5 (mean 0.6). The tritan axis was the one most affected by cataract. There was no significant difference between cataract sub-groups. Also, the central colour contrast sensitivity was affected by cataract. Again, the tritan axis was the most affected one. There was no significant difference between the cataract sub-groups. We also found large and significant differences in central colour contrast thresholds between normal subjects and postoperative values from the cataract group in all colour axes. The colour contrast sensitivity was poorer in pseudophakes than in normals. There was a difference between the three groups of different IOL material used (PMMA, acrylic and silicone). The difference was significant in the protan axis, the acrylic group having the best colour contrast sensitivity.

Conclusion: Peripheral colour contrast sensitivity was affected by cataract, even when only moderately developed. This finding is of importance and should be considered when the method is used to study other eye diseases e.g. glaucoma. Central colour contrast sensitivity was also affected by cataract. The pseudophakes were found to have poorer colour contrast sensitivity than normals. The material in the IOL seemed to be of importance for colour contrast.

Purpose: To study possible differences in colour contrast sensitivity between different intraocular lens (IOL) materials with consecutive same day cataract surgery performed in the right and left eyes.

Methods: Central colour contrast sensitivity was measured with a computer graphics system along the protan, deutan and tritan axes. Thirty-four patients with cataract were studied. The patients were randomized to one of three groups: group 1 received a Clariflex (silicone) lens in one eye and an Akreos Fit (hydrophilic acrylic) lens in the other; group 2 received an Akreos lens in one eye and a Sensar AR40e (hydrophobic acrylic) lens in the other, and group 3 received a Clariflex lens in one eye and an AR40e lens in the other. Surgery was performed in both eyes on the same day. A postoperative questionnaire was distributed, asking the patients to describe any differences experienced between their two eyes.

Results: There were no significant differences between the three different IOLs in any colour axis. There were no complications of importance during surgery. Thirty-two of the 34 patients answered the questionnaire. Twenty-one patients experienced some difference between their two eyes in distance vision and 23 noticed differences in near vision. For distance vision, nine reported better vision in the eye with the Akreos IOL, eight in the eye with the Clariflex IOL lens and four in the eye with the AR40e IOL. For near vision, 12 preferred the Akreos lens, eight the Clariflex lens and three the AR40e lens.

Conclusion: There were no significant differences between the three different IOLs in any colour axis.

AIM To compare the intraocular pressure (IOP) reducing effect of latanoprost 0.005% and 0.001%.

METHODS Twenty four patients with glaucoma or ocular hypertension were randomised into two groups. Twelve patients (group 1) were given latanoprost 0.005% once daily for 4 weeks and then latanoprost 0.001% once daily for the following 4 weeks. Twelve patients (group 2) were given latanoprost 0.001% once daily for 4 weeks and then latanoprost 0.005% for the following 4 weeks.

RESULTS There was a significant IOP reduction from baseline in both groups on day 28 as well as on day 56. When the results from both groups were used for calculations, the mean IOP reduction from baseline after 4 weeks of treatment with latanoprost 0.005% (day 28 or 56) was 9.6 (SD 3.3) mm Hg (35.0%). After 4 weeks of treatment with latanoprost 0.001%, the IOP reduction (day 28 or 56) was 7.6 (3.4) mm Hg (27.7%). The difference in IOP reduction between the two concentrations was 2.0 (2.3) mm Hg (p<0.001).

CONCLUSIONS Latanoprost 0.005% was more effective than latanoprost 0.001% in reducing IOP. Even the lower concentration was surprisingly effective, and potentially may be of importance for use in clinical practice. Furthermore, it is at present unknown whether the increase in iris pigmentation seen in certain patients treated with latanoprost 0.005% is dose dependent and might be less pronounced with latanoprost 0.001%. Long term studies with a larger number of patients are required in order to answer this question.

Objective.  —To evaluate the effects of PhXA41, a new prostaglandin analogue, on the intraocular pressure (IOP) in patients receiving pilocarpine treatment and the effects of pilocarpine in patients receiving PhXA41 treatment.

Design.  —Twenty patients with ocular hypertension were randomized into two parallel groups. The treatment period was 2 weeks. Ten patients in group 1 were given PhXA41 twice daily during week 1 and, in addition, pilocarpine three times daily during week 2. Ten patients in group 2 received pilocarpine three times daily during week 1 and PhXA41 twice daily in addition during week 2. PhXA41 was used in a concentration of 0.006%, and pilocarpine was given in a concentration of 2%.

Main Outcome Measures.  —In group 1, the mean IOP on day 0 was 25.1 mm Hg; on day 7,19.1 mm Hg; and on day 14,17.6 mm Hg. In group 2, the mean IOP on day 0 was 23.8 mm Hg; on day 7,20.4 mm Hg; and on day 14,17.7 mm Hg.

Results.  —PhXA41 had a clinically significant IOP-lowering effect (23.4% reduction on day 7 as compared with baseline day (P<.001). The corresponding value with pilocarpine was 14.3% (P<.001). When pilocarpine was added to PhXA41, the additional IOP reduction was 7.4% (P<.01) compared with 14.2% (P<.01) when PhXA41 was added to pilocarpine. The two groups were found to have an almost equal reduction in IOP on day 14 (group 1,29.4%; group 2, 26.6%). No serious adverse reactions were seen. Some conjunctival hyperemia in the PhXA41-treated eyes was noted on day 7, as compared with the pilocarpine-treated eyes, but there were few complaints of discomfort.

Conclusions.  —This study indicated that PhXA41 could be useful in the treatment of glaucoma, as monotherapy, or in certain cases in combination with pilocarpine.

Purpose: To study the expression of basic fibroblast growth factor (bFGF) in the early phases of corneal wound healing in the presence or absence of granulocytes. Methods: A central penetrating corneal alkali wound was inflicted to one eye in each of 14 rabbits under general anaesthesia. Subsequently, seven of the rabbits were given fucoidin i.v. for 36 hours in order to block the selectins on the vascular endothelium, thus preventing blood granulocytes from entering the tissues. Then, corneas were prepared, stained for bFGF and evaluated by light microscopy. Results: Whereas normal corneal epithelium expressed bFGF weakly, conjunctival epithelium did so strongly, particularly the goblet cells. The corneal endothelium showed medium staining, while keratocytes and vascular endothelial cells did not consistently express bFGF. After 36 hours of wound healing, a marked upregulation of bFGF expression was observed in the corneal epithelial and endothelial cells, as well as in the keratocytes, that were migrating into the wound. No other changes were noted. None of these features were modulated when granulocyte emigration was prevented by fucoidin administration. Conclusions: The difference in bFGF expression between the corneal and conjunctival epithelium suggests a role for this growth factor in the barrier function at the limbus. Moreover, the specific presence of bFGF in cells migrating into the wound indicates the participation of bFGF in corneal wound healing. Expression of bFGF was independent of granulocytes. Copyright © Acta Ophthalmol Scand 2005.

Purpose: To map the proliferative activity of corneal cells during wound healing following photorefractive keratectomy (PRK) and to compare two markers for proliferation. Methods: PRK, 5- mm in diameter with a -6 D setting, was performed in one eye of 28 New Zealand White Rabbits. The rabbits were sacrificed at time points between 12 hours and three months after surgery. The treated and fellow corneas were fixed in 10% formaldehyde, paraffin embedded, and immunohistochemically stained for proliferate cell nuclear antigen (PCNA) and at one time point, 1 week, also for Ki-67. Results: Following initial sliding of the epithelial cells, the proliferative activity in the wound area starts in the leading edge (24 hours) and is spread towards the periphery. The proliferative activity peaks after one week and subsides during the following two weeks. Early (24 hours) proliferative activity is also seen in the limbal epithelium which peaks after three days. The keratocytes express PCNA in the peripheral stroma 48 hours after injury. They then also migrate to repopulate the stroma under the wound area. The expression period lasts 1 week and subsides the following week. Leukocytes are found in the wound as early as 12 hours after injury. The cells disappear around the time of epithelial wound closure, i.e. after 3 days. The two proliferative markers PCNA and KI 67 show a similar distribution after surgery. Conclusion: Epithelial proliferative activity starts earlier after injury, and is preceded by leukocyte presence in the wound. The PCNA expression starts later in the keratocytes but lasts somewhat longer (3 weeks). PCNA expression appears more efficient than Ki-67 to show proliferative activity of slow cycling cells in the cornea.

The electroretinograrn (ERG) reflects the summation of electrical responses generated by neurons and non-neuronal cells in the retina and pigment epithelium in response to light. The major ERG components are the fast, negative a-wave, the fast, positive b-wave and the slow, positive c-wave. The ERG is superimposed on the standing potential of the eye (SP).

Experiments were performed on albino and pigmented rabbits under general anesthesia. The aim was to study the development of the ERG with time in response to repeated light stimuli of different intensities (Paper I) or different interstimulus intervals (Paper II). The effects of a prolonged uniocular dark adaptation period (Paper III) and the influence of possible diurnal rhythms (Paper IV) were investigated, as was the long-term development and reproducibility of the ERG in experiments performed on consecutive days (Paper V). The influence of intravitreally injected dopamine at different concentrations on the development of the ERG was also studied (Paper VI).

When using light stimuli of high intensity and short interstimulus interval (Papers I and II) the c-wave amplitude was immediately reduced after the first stimulus, but recovered to a large extent. The parallel behavior of the c-wave and SP suggested the presence of a pigment epithelial mechanism behind the recovery of the c-wave. The a- and b-wave amplitudes were immediately reduced, but recovered only to a limited extent. The final amplitudes of the b-and c-waves and to a large extent also of the a-wave seemed to be fairly independent of stimulus intensity.

When one eye was dark adapted and the other eye simultaneously exposed to repeated widely spaced light stimuli of moderate intensity (Paper III) the b- and c-wave amplitudes of the unoccluded eye slowly increased during the course of several hours, but the a-wave amplitude was more stable. When the cover was removed from the previously occluded eye the a- and b-wave amplitudes immediately attained the level of those recorded from the contralateral eye, which had been light adapted by the stimuli. The phenomenon may suggest a mechanism for transfer of information between the eyes.

The development of the ERG amplitudes and the SP was studied during the course of the day by repeating identical series of light stimuli every hour, and by commencing the experiments at different points of time (Paper IV). The amplitude of the b-wave did not reach relative stability until 2.5 to 3.5 hours after the beginning of dark adaptation, and that of the cwave continued to rise throughout the experiments. Since the pattern was similar in experiments starting in the morning and in the afternoon, it seems less probable that diurnal rhythms caused the findings.

The long-tenn development of the ERG during several hours of stimulation with light of high intensity was studied in identical experiments performed on consecutive days (Paper V). In addition to the findings described in Papers I and II, a peak in the b-wave amplitude was observed 20-21 min after the start of light stimulation. There were no significant differences between experiments performed on consecutive days.

The effects of intravitreally injected dopamine of different concentrations on the development of the ERG was studied in Paper VI. During exposure to repeated light stimuli of moderate intensity the b- and c-wave amplitudes were reduced with a decreased or even abolished amplitude increment with time in the eye injected with dopamine, and the responses were related to the concentration of the drug. The peaks in the b-and c-wave amplitude seen in the control eye when frequent stimuli of high intensity were used were abolished in the eye injected with dopamine at higher concentrations of the drug. Thus, dopamine may affect the adaptive process of the retina.