[Corneoretinal dystrophy (Bietti)-- Long-term course of one patient over a period of 30 years, and interindividual variability of clinical and electrophysiological findings in two patients]. / Kristalline korneoretinale Dystrophie (Bietti) - Langzeitverlauf von einem Patienten von 30 Jahren und interindividuelle Variabilität klinischer und elektrophysiologischer Befunde von zwei Patienten12.

BACKGROUND: A tapetoretinal dystrophy with crystalline deposits of the retina and limbal cornea was described by Bietti in 1937. To date, only a few cases with long-term follow up have been reported. PATIENTS AND METHODS: Two patients are presented including the clinical findings, fluorescein angiography, electrophysiology [electroretinography (ERG); electrooculography (EOG), multifocal electroretinography (MERG)], adaptometry, and transmission electron microscopy (TEM) of peripheral blood lymphocytes. The clinical findings were at least in part documented over a period of 30 years. RESULTS: The most striking features were deposits in the retina and cornea associated with crystalloid lysosomal inclusions in peripheral lymphocytes, and choroidal atrophy especially in advanced stages of the disease. The light rise (EOG), rod- and cone-driven responses (ERG), the responses of the MERG and visual fields were affected progressively during the course. These advanced changes of the retinal pigment epithelium and choriocapillaris were observed in the 2(nd) decade already. CONCLUSIONS: The findings of deposits in the cornea, retina and lymphocytes may help to differentiate BCD from other chorioretinal dystrophies. The results confirm a variable course in clinical expression of BCD between individuals.

[A clinicopathological study of 297 cases of retinoblastoma].

OBJECTIVE: To find a morphological criterion of classification for choroidal invasion of retinoblastoma in order to further study clinical pathology of retinoblastoma (Rb) under an integrate rule. METHODS: The changes of retinal pigment epithelium, Bruch's membrane and choroid on histopathological sections of primarily enucleated eyes with Rb in 297 cases were observed under a light microscope. RESULTS: The globe wall invasion could be morphologically divided into four stages (briefly pigment epithelium-choroid classification). Stage I: Only retinal pigment epithelium was infiltrated, the Bruch's membrane was intact. Stage 2.: The Bruch's membrane was destructed, but the choriocapillaries were not invaded. Stage 3: The invasion reached middle choroidal blood vessels close to the choriocapillaris in a limited scope. Stage 4: Massive choroidal infiltration of all choroidal layers existed and the sclera could be simultaneously involved. The mortality for stage 4 was 11.5% and for stage 1 to 3 was 0.4%. CONCLUSION: The pigment epithelium-choroid stage (PEC-stage) classification in our study can be used as an integrate rule to compare the invasion degree of retinoblastoma in different individuals and studies.

[Morphologic classification of choroidal invasion of retinoblastoma]. / Histomorphologische Stadieneinteilung des infiltrativen Wachstums in der Aderhaut beim Retinoblastom.

In order to inquire into standard for morphologic classification of choroidal invasion of retinoblastoma and to study the tumor clinic--pathologic further under the integrated scale, the changes of retinal pigment epithelium, Bruch's membrane and choroid on the histopathological sectins of 297 cases of primary enucleated eyes of retinoblastoma were retrospectively observed under the light microscopy. The choroidal invasion was morphologically divided into four stages: Stage 1, only retinal pigment epithelium involved, the Bruch's membrane was intact; Stage 2, the Bruch's membrane was destroyed and the choroidal capillaris was not infiltrated; Stage 3, choroial capillary and middle blood vessel layer in small limits were infiltrated; Stage 4, invasion involved in choroid in great limits and involvement of sclera existed simultaneously. This classification (also called pigment epithel--choroid stage, PEC--stage) reflected both infiltrated procedure of tumor cells and preventive mechanism in eye and morphological criterion half--quantitatively. It can be used as a united standard to compare the infiltration degree of retinoblastoma among different individuals and different studies.

The formation of type-I concretions in Drosophila Malpighian tubules studied by electron microscopy and X-ray microanalysis.

There are two types of concretions in Drosophila Malpighian tubules: Type-I concretions originate in the distal segments of the anterior tubules, type-II concretions in the adjacent transitional segment between the apical microvilli. Type-I concretions are formed with the aid of carbonic anhydrase within intracellular vesicles, which migrate to the apical cell membrane where they are discharged into the lumen by exocytosis. The carbonic anhydrase inhibitors acetazolamide or hydrochlorothiazide prevent the formation of concretions by interruption of bicarbonate supply. In addition, the formation of concretions can be reduced by feeding with sodium cellulose phosphate.

Ruthenium-106 brachytherapy for peripheral retinal capillary hemangioma.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ruthenium-106 brachytherapy of large peripheral retinal capillary hemangiomas. DESIGN: A retrospective case series. PARTICIPANTS: In 25 eyes of 24 patients, peripheral capillary retinal hemangiomas were treated. INTERVENTION: Brachytherapy using 106-ruthenium/106-rhodium plaques was performed. MAIN OUTCOME MEASURES: Eyes were reviewed for hemangioma regression after brachytherapy, occurrence of retinal detachment, requirement of additional vitreoretinal surgery, final visual outcome, and final retinal status. RESULTS: Preoperative mean visual acuity of all eyes treated was 20/60, mean hemangioma diameter was 3.8 mm, corresponding to approximately 2 disc diameters. In 14 eyes, the retina was attached before surgery, 8 eyes showed an exudative detachment, and 3 eyes showed a traction detachment. Fifteen patients had definite von Hippel-Lindau syndrome. Twenty-three of 25 hemangiomas could be destroyed by single brachytherapy. In 16 eyes, a favorable outcome could be achieved. In nine eyes, outcome was unfavorable, characterized by a severe drop in visual acuity, a persisting exudative retinal detachment, or a recurrent traction detachment. In one eye requiring repeated brachytherapy, irradiation retinopathy occurred. Hemangiomas up to a size of approximately 5.0 mm without preoperative exudative detachment could be treated safely by brachytherapy, whereas a larger hemangioma size or a pre-existing exudative retinal detachment predisposed to an unfavorable outcome. CONCLUSION: Solitary peripheral retinal hemangioma can be ablated effectively by ruthenium-106 brachytherapy. A favorable outcome can be expected if the hemangioma diameter is 5.0 mm or smaller and if there is no preoperative exudative retinal detachment.

Retinal plasma extravasation in animals but not in humans: implications for the pathophysiology of migraine.

High-intensity electrical stimulation of the trigeminal ganglion is accompanied by mast cell degranulation, vasodilatation, increased endothelial permeability and leakage of albumin from postcapillary venules within the dura mater. Overall, the histological appearance suggests an evolving sterile inflammatory response. This neurogenic inflammation within the meninges has been suggested as a model to explain the pain in migraine and cluster headache, and has been used to characterize the pharmacology of anti-migraine compounds. Using the rat model of neurogenic inflammation, the albumin extravasation ratio (stimulated : unstimulated side) in vehicle-treated animals in the dura and retina was 1.60 +/- 0.11 and 1.76 +/- 0.18, respectively (n = 10; values are mean +/- SEM). Pretreatment with sumatriptan (n = 9) produced a highly significant reduction in the ratio of extravasation within the dura to 1.10 +/- 0.06 (P = 0.002) and in the retina to 0.96 +/- 0.06 (P = 0.001), as did the neurokinin-1 receptor antagonist RP 67580 (n = 12) in the dura (1.04 +/- 0.11, P = 0.002) and retina (1.08 +/- 0.06, P = 0.001). These data demonstrate increased endothelial permeability and leakage of albumin not only in the dura but also in the retina. In a second stage we investigated possible extravasation in the human retina in acute migraine (n = 8) and cluster headache (n = 5) using fluorescein or indocyanine angiography. No increased endothelial permeability or leakage of dye could be found in the human retinal or choroidal vessels during headache attacks or in the headache-free interval in persons suffering from both migraine and cluster headache. These data raise the possibility that neurogenic inflammation is not a major factor in headache attacks in migraine or cluster headache.

Long-term results after low dose ocular irradiation for choroidal haemangiomas.

AIM/BACKGROUND: The most common choice of treatment for choroidal haemangiomas (CH) in the past has been the employment of scatter photocoagulation of the surface. This management often requires repetitive treatment or additional invasive management due to massive exudative detachment of the retina. The aim of this retrospective study was to investigate the outcome of the alternative application of low dose external beam irradiation with high energetic photons on these tumours. METHODS: A total absorbed dose of 20 Gy was applied to a total of 51 symptomatic eyes: 36 with a circumscribed CH of the posterior pole and 15 with diffuse CH as part of the Sturge-Weber syndrome. The indication for treatment was an exudative retinal detachment including or threatening the fovea. The mean follow up times in each group were 4.5 and 5.3 years, respectively. Out of a group of 33 patients from whom reliable data could be derived, 17 had symptoms lasting longer than 6 months. RESULTS: In 23 cases (63.8%) with circumscribed CH complete resolution of the subretinal fluid was achieved; the remaining 13 cases (36.2%) showed residual serous detachment distant to the fovea. The visual acuity improved by two or more lines in 14 cases (38.9%), remained stable in 14 cases (38.9%), and decreased in eight cases (22.2%). The functional success was dependent on the lag duration between onset of first subjective symptoms and treatment. The morphological results with diffuse CH were similar to those of the group of circumscribed CH. The visual acuity (VA) at last examination was improved in seven cases (46.6%); in the remaining eight cases, VA was unchanged or had deteriorated. The poor functional outcome in the latter was mainly attributable to secondary glaucoma. CONCLUSION: External beam irradiation is a useful and a low invasive therapeutic option for CH. A successful functional outcome is dependent on the time delay between first onset of symptoms and the beginning of therapy, the formation of subretinal fibrosis, and also on secondary glaucoma in the case of Sturge-Weber syndrome.

[Cryocoagulation in therapy of proliferative diabetic retinopathy]. / Die Kryokoagulation in der Therapie der proliferativen diabetischen Retinopathie.

BACKGROUND: The importance and indication of panretinal photocoagulation in proliferative diabetic retinopathy is well established. In contrast the indication of cryotherapy in this disease is more controversial especially in regard of new indications for early vitrectomy. The present study was performed to characterize the clinical possibilities and limitations of cryotherapy in complicated proliferative diabetic retinopathy. PATIENTS AND METHODS: In 231 patients with proliferative diabetic retinopathy and vitreous hemorrhage limiting further photocoagulation the visual outcome and diabetic retinal changes were observed before and after cyrotherapy (15-20 effects) of the ophthalmoscopically visible peripheral retina. RESULTS: After cryotherapy regression of active proliferations could be seen in 70% of the patients. Resorption of vitreous hemorrhages could be found in 80% of the patients. This was associated with improvement in visual acuity in 50-60% of the patients. Loss of vision was caused due to tractional detachment in 20% of the patients and due to further vitreous hemorrhages in 10% of the patients. Comparison of retinal changes between patients with worsened visual acuity and patients with increase in visual acuity demonstrated the preoperative fibrotic status of disc neovascularisation as the most important prognostic factor. The development of central tractional detachment was significantly higher in patients with preoperatively partly regressed disc neovascularisation. CONCLUSIONS: Cryotherapy of the peripheral retina in proliferative diabetic retinopathy with vitreous hemorrhages is therefore only indicated after ophthalmoscopical or echographical exclusion of peripapillary fibrosis and retinal traction and with sufficient visibility of the peripheral retina for the application.

Carbonic anhydrase supports electrolyte transport in Drosophila Malpighian tubules. Evidence by X-ray microanalysis of cryosections.

Electron probe X-ray microanalytical studies on the role of carbonic anhydrase in electrolyte transport in the cells of Drosophila Malpighian tubules indicate that carbonic anhydrase delivers protons and bicarbonate ions to ion transport systems in the cell membrane. After injection and after feeding acetazolamide or hydrochlorothiazide, known inhibitors of carbonic anhydrase, the contents of potassium, magnesium and chloride in the apical cytoplasm and in the cytoplasm close to the basal plasma membrane decreased. We explain our measurements by the hypothesis of a basal Mg-H-antiport system in parallel with Cl-HCO(3)-antiport, inhibitable by DIDS. Zinc is supposed to enters cells and intracellular Zn storage vacuoles by a negatively charged Zn-anion-complex in exchange for HCO(3)(-) ions. This antiport is inhibitable by SITS. The content of the Zn storage vacuoles is acid, as shown by red fluorescence after incubation of Malpighian tubules with acridine orange. Red fluorescence is absent after preincubation in a medium containing an inhibitor of carbonic anhydrase. Carbonic anhydrase was demonstrated cytochemically in the Golgi-ER complex, Golgi vesicles and intercellular space. We suppose that carbonic anhydrase is synthesized and stored in the Golgi-ER-complex from where it is released into the tubule lumen.

[Retinitis pigmentosa--clinical, genetic and pathophysiologic aspects]. / Retinitis pigmentosa--klinische, genetische und pathophysiologische Aspekte.

Retinitis pigmentosa defines a genetically heterogenous group of disorders characterized by degenerations of photoreceptors and pigment epithelium. This article reviews our current knowledge of the genetical, clinical and pathophysiological aspects of this disease complex. Therapeutic concepts under current investigation are discussed as well. In recent years tremendous new insights have been made using molecular techniques for the investigation of retinal dystrophies. Ophthalmoscopically very similar patterns of photoreceptor dystrophies have been related to different gene mutations. In contrast, mutations in a single gene may cause different clinical patterns of photoreceptor dystrophies. Therefore, these recent results suggest that a reclassification of retinal dystrophies on the basis of their genetic origin may be favourable. In the future molecular genetics and the recent developments may play an increasing role for clinical classification and evaluation of photoreceptor dystrophies. The continued clinical and experimental research on hereditary disorders may help to elucidate further the wide disease spectrum and thereby developing new classifications and efficient therapeutic concepts.

[Focal proliferations of retinal pigment epithelium. Risk factor in senile macular degeneration]. / Fokale Proliferationen des retinalen Pigmentepithels. Risikofaktor bei der altersabhängigen Makuladegeneration.

BACKGROUND: Clinical studies have demonstrated the relevance of focal RPE proliferations in early AMD as risk factors for visual loss caused by late AMD. Angiographically these focal RPE proliferations are characterized as small hypofluorescent spots with hyperfluorescent rim without leakage. Corresponding to histological and experimental studies they can be interpreted as small areas of occult choroidal neovascularizations covered by proliferated RPE cells. The characterization of the long-term prognosis of these lesions was the aim of the present study. PATIENTS AND METHODS: Ninety-eight patients (52 female, 46 male) were reexamined clinically and angiographically with a follow-up of 2-12 years (mean 6.5 years). RESULTS: Visual loss of two lines or more could be observed in 64.5% of patients with final visual acuity less than 20/100 in 24.5% of patients. Morphologically the changes in visual acuity were related to the progression towards classical choroidal neovascularizations in 32.7% of patients. In addition 11.2% of patients demonstrated a regression of the small occult membrane with the development of small areas of RPE atrophy covering the size of the original occult neovascularization. In 10.2% of the patients enlargement of the lesion was observed, resulting in a large occult choroidal neovascularization without signs of classical membranes, and in 45.9% of patients the clinical and angiographical situation was unchanged. The most important prognostic factor correlating with visual loss was the presence of a disciform lesion in the fellow eye and of multiple drusen in the examined eye. Other factors like the size or location of the focal RPE proliferation and the duration of follow-up did not correspond with visual loss. CONCLUSIONS: Focal RPE proliferations in early AMD interpreted as small occult choroidal neovascularizations are associated with a high risk of visual loss. Especially if these lesions are associated with multiple drusen and a disciform lesion in the fellow eye, nearly all patients are at risk for visual loss. These changes may therefore characterize a special high-risk group for future prophylactic treatments in early AMD, but because of the high risk for the development of classical choroidal neovascularizations in this group, these results are also very important for the planning of prophylactic laser trials for drusen in early AMD.

[Change in hole size and area of retinal detachment after pars plana vitrectomy in Gass stage III macular foramina]. / Anderung der Lochgrösse und des abgehobenen Netzhautbereichs nach Pars-plana-Vitrektomie bei Makulaforamen im Stadium III nach Gass.

UNLABELLED: In 15 patients with a stage III macular hole a pars plana vitrectomy with membrane peeling was performed. At the end of the operation a gas/air exchange was performed and patients had to lie face down for some days. METHODS: Before and 4-7 months after the operation a picture of the posterior pole was taken with a Zeiss fundus camera. Pictures were digitized, and the area of the hole and of the surrounding detached retina was measured using a special image analyzer software. RESULTS: In seven cases an improvement of visual acuity was found; in the remaining eight cases visual acuity remained unchanged. In five cases (33%) the retina was totally attached around the hole. In eight cases the detached area had become smaller, in two cases larger, and in two cases we could no longer observe the rim of the hole. In the remaining cases the area of the holes changes by less than 10%. CONCLUSIONS: The results show that even in cases where total attachment of the surrounded retina cannot be achieved, reduction of the detached area can be expected in most cases. Simultaneously, a reduction of metamorphopsia can be observed. However, the improvement of visual acuity is not very high. That is why we will perform pars plana vitrectomy in stage III holes only in exceptional cases.

[Observations of different presentations of choroid neovascularization in indocyanine green angiography]. / Beobachtungen zur unterschiedlichen Darstellung choroidaler Neovaskularisationen in der Indozyaningrün Angiographie.

The interpretation of choroidal neovascular membranes (CNV) in indocyanine green angiography (ICG-A) is difficult. It is not known whether demarcated hyperfluorescence in the ICG-A reliably reflects the true morphology and the total extent of a CNV. Therefore, in this retrospective study, the patterns of fluorescein and ICG angiograms were evaluated and compared in both occult and well-defined CNV. In 153 out of a total of 168 cases with CNV, age-related macular degeneration (AMD) was the underlying disease. CNV was occult in 114 and well-defined in 39 cases. The angiographic examinations with both dyes were performed with a modified fundus camera combined with a digital imaging system. In the group of AMD patients with occult or ill-defined CNV. 42 cases (36.8%) showed a defined membrane in the ICG stain. The filling patterns of ICG were extremely variable. In the group of AMD patients with classic CNV, ICG-A showed evidence of staining in the early and late phase in 14/39 cases (36%), exclusively in the early phase in 5/39 (13%) cases and only in the late phase in 17/39 cases (44%). Surprisingly, three well-defined membranes in fluorescein angiography (FLA) were not seen in any phase of the ICG-A. Compared with FLA, the 17 CNVs with demarcation only in the late phase of the ICG-A were seen to be larger in 8 and smaller in 9 cases while all CNVs seen in the early phase, or in both early and late phase, were of identical size with the early fluorescein staining. The pattern of ICG staining of CNV is complex. The single finding of a demarcated hyperfluorescence in the late phase of ICG-A should be interpreted with utmost caution, particularly in regard to planning laser therapy.

[Fluorescence angiography in age-related macular degeneration. Study of the incidence of lesions treatable with coagulation]. / Fluoreszenzangiographie bei der altersabhängigen Makuladegeneration. Studie zur Häufigkeit koagulativ behandelbarer Läsionen.

BACKGROUND: The treatment of late age-related Macular Degeneration (AMD) according to the results of prospective clinical studies is indicated in classical choroidal neovascularisations (NV), which can be delineated from the center of the fovea. To evaluate the effectiveness of this therapy, the knowledge of the frequency of treatable lesions in the spectrum of late AMD is important. PATIENTS AND METHODS: The frequency of different manifestations of late AMD and of lesions treatable with photocoagulation according to the results of prospective clinical studies was recorded in a consecutive series of 2503 fluorescein angiogramms in patients with symptomatic late AMD. RESULTS: Classical choroidal NV could be detected in 35.4% of the patients. In 5.5% of the patients these NV were extra- or juxtafoveolar and therefore laser treatment could be recommended. 10.2% of the patients demonstrated small (< 1 PD) subfoveal classical NV and 20.4% of the patients showed large (> 1 PD) subfoveal NV or membranes associated with large subfoveal, subretinal hemorrhages. Occult choroidal NV could be seen in 41.8% of the patients. These occult NV were larger 1 PD in 21.9% of the patients and small (< 1 PD) in 19.9% of the patients. Pigment epithial detachments (PED) could be seen in 14.6% of the patients (9.9 vascular PED, 3.7% avascular PED, 1.0% rip of the retinal pigment epithelium). Disciform scars were present in 7.2% of the angiogramms. CONCLUSIONS: The spectrum of late AMD can be differentiated in several clinical features. In this consecutive series of 2503 symptomatic AMD patients only appr. 6%% of the patients could be treated with laser treatment according to the results of prospective clinical studies. Because in addition the success of this treatment is very limited, the development of new therapeutic options is one of the major tasks in ophthalmology.

[Clinical experiences after implantation of various lens types in silicon oil tamponade]. / Klinische Erfahrungen nach Implantation verschiedener Linsentypen bei Silikonöltamponade.

BACKGROUND: A tamponade of the vitreous space with silicone oil will obligatory lead to cataract after 6 to 12 months. Today it is easily possible, to implant an artificial lense in silicone oil filled eyes. However the combination of an artificial lense and silicone oil will lead to a strong inflammation in the anterior segment of the eye. PATIENTS AND METHODS: 22 pseudophacic patients with silicone oil tamponade were examined 2 to 6 months after the operation. In 12 patients simple artificial lenses were implanted, in 10 patients heparin modified lenses were implanted. In 10 cases the lens was implanted followed by the insufflation of silicone oil in the vitreous cavity, in 2 cases a lens was implanted in a silicone oil filled eye and the silicon oil was not removed. In 8 cases the implantation of the artificial lens has been performed some months to years before the insufflation of the silicone oil. The indication for the silicon oil tamponade was a PVR retinal detachment in all cases. The following parameters were examined: Reaction of the pupil to light, pupil round or oval in miosis, examination of the fundus peripherie possible after mydriasis, fixation of the iris with parts of the capsula or with the anterior surface of the lens? In addition in 12 cases the postoperative refraction was compared with the results of the biometry, which was performed before the operation. RESULTS: In the cases with a simple lens in about 50% an incomplete miosis or an oval pupil because of fixation of the iris with parts of the capsula or with the anterior surface of the lense could be observed. In the cases with heparin modified lenses these complications could be observed in 20%. In all cases a strong opacification of the capsula was seen. In 8 of 12 cases with combined procedure a small hyperopia was measured, in 4 cases a large deviation was measured. CONCLUSIONS: The implantation of an artificial lens in silicone oil filled eyes is an alternative to the aphacic status with an Ando Iridectomy. Obviously heparin modified lenses have advantages in these cases. Because of the strong cataract formation we suggest to remove the anterior and the posterior capsula in the first operative session and to implant the haptics of the lens into the sulcus. Because of the high rate of complications generally first a stable retina condition should be reached before the implanation of an artificial lens is performed.

Long-term results of pars plana vitrectomy in the management of intermediate uveitis.

Pars plana vitrectomy is a useful tool for the management of certain complications in chronic intermediate uveitis. Media opacities obscuring the visual axis, vitreous membranes causing tractional retinal detachment, macular puckers, and ciliary traction leading to hypotony are clear indications for this approach. Furthermore, it has been suggested that vitrectomy may have a favorable long-term effect on the course of disease. The procedure may achieve regression of inflammation, tapering of immunosuppression, and improvement of cystoid macular edema. However, randomized prospective trials are still needed to define the role of vitrectomy in altering the course of uveitis.

[Long-term outcome of radiotherapy of choroid hemangioma]. / Langzeitresultate der Strahlentherapie von Aderhauthämangiomen.

The usual therapeutic approach to circumscribed choroidal hemangiomas of the posterior pole consists of scatter photocoagulation of the tumor surface. This may often require repetitive treatment or additional invasive measures prior to coagulation due to massive exudative detachment of the retina. In this study, external beam irradiation with high-energy photons (total absorbed dose: 20 Gy) was applied to 36 symptomatic patients. The indication for treatment was exudative retinal detachment including or threatening the fovea. The mean duration of follow-up was 4.5 years (4 months to 24 years, median 4 years). In 23 cases (63.8%) complete resolution of the subretinal fluid could be achieved; 13 cases (36.2%) showed residual serous detachment at some distance from the fovea. The visual acuity improved by two or more lines in 14 cases (38.9%), remained stable in 14 cases and decreased in only 8 cases (22.2%). The functional success was dependent on the interval between onset of first subjective symptoms and treatment. External beam irradiation is a successful form of treatment for choroidal hemangiomas.