[Retinal detachment in children and adolescents. Specific clinical features]. / Ablatio retinae bei Kindern und Jugendlichen. Spezifische Befundmerkmale.

BACKGROUND: Due to the long life expectancy, retinal detachment is a special threat to visual acuity in children and adolescents. This study presents the clinical features of retinal detachment in childhood and adolescence up to the age of 20 years. PATIENTS AND METHODS: A cohort was selected comprising 259 patients who suffered from unilateral or bilateral retinal detachment, were not older than 20 years of age at the first diagnosis of the first or only affected eye and had undergone surgery at least once at the Department of Ophthalmology of the University Medical Center of Munich during a period of 18 years (1980-1998). This patient collective was retrospectively analyzed with respect to the clinical features of the first retinal detachment. The group consisting of only one affected eye or the first affected eye (259 eyes) was included. The fellow eyes affected later were excluded (19 eyes). RESULTS: The time period between the first visual symptoms and the diagnosis of retinal detachment was on average 9.6 weeks and the most commonly manifested symptom was loss of vision (36.3% of patients). In 40.2% of the patients the detachment was discovered fortuitously. The most frequent presentation (34.0%) was a 2-quadrant retinal detachment and was (sub)total in 27.0% of eyes. Macular detachment was found in 154 eyes (59.5%). The commonest type of retinal break was a tear near the ora serrata (36.1% of all breaks). Giant tears (12.8% of all breaks) occurred preferentially in the area of the ora serrata, round atrophic holes were identified especially in the area of the equator, often in the form of a chain of holes. Breaks most frequently occurred in the inferior temporal quadrant. In 22.4% of retinal detachments no break was found even intraoperatively. A primary proliferative vitreoretinopathy (PVR) of at least stage C was involved in 25.5% of detachments. CONCLUSION: In childhood and adolescence a characteristic delay of diagnosis enables a large sized expansion of the retinal detachment with frequent macular involvement and a high proportion with (sub)total detachment and severe primary PVR. Tears in the ora serrata area, giant tears, multiple round atrophic holes in the area of the equator and a high rate of undetectable breaks are the intrinsic characteristics of juvenile retinal detachment.

[Clinicopathological correlations at the vitreoretinal interface]. / Klinisch-pathologische Korrelationen an der vitreoretinalen Grenzfläche.

BACKGROUND: Clinicopathological studies of the vitreoretinal interface (VRI) improve our understanding of the pathogenesis of vitreal maculopathy, facilitate differential diagnoses and help to develop new treatment strategies. OBJECTIVE: The aim of the study was to provide a comprehensive overview on clinicopathological correlations of the VRI. METHODS: A semi-structured literature search was performed in the Medline and Embase databases for relevant original studies on clinicopathological correlations of vitreal maculopathy, in addition to the latest books and review articles. RESULTS: Age-related vitreous changes with persistent vitreomacular adhesions on the retinal surface promote cellular migration and proliferation onto the vitreal side of the internal limiting membrane (ILM), thereby cementing the vitreomacular adhesions and strengthening the traction forces on retinal layers. Cellular or fibrocellular proliferation at the vitreomacular interface can be seen in all vitreal maculopathies. Furthermore, vitreoschisis in the context of anomalous posterior vitreous detachment causes the presence of vitreous cortex collagen fibrils on the vitreal side of the ILM which is associated with epiretinal membrane formation. Glial cells, hyalocytes and myofibroblasts represent the major cell types in the epiretinal cell proliferation. Glial cells and hyalocytes are capable of transdifferentiation into myofibroblasts which possess strong contractive properties and are well known for the production of extracellular matrix components. CONCLUSION: Removing vitreomacular adhesions and vitreous cortex collagen fibrils from the retinal surface is most important for successful treatment. In cases with epiretinal cell proliferation, however, removal of the ILM during macular surgery is mandatory to avoid reproliferation and recurrence. Improving the detection of epiretinal cell proliferation and cell distribution in patient eyes by optical coherence tomography or by introduction of new technologies should be addressed in the future.

[Pharmacological vitreolysis]. / Pharmakologische Vitreolyse.

BACKGROUND: The vitreous plays an important role in the development and progression of vitreoretinal diseases. Vitrectomy is the treatment modality of choice in these cases. However, mechanical vitrectomy is incomplete. Therefore, alternative strategies have been pursued including pharmacological means such as enzymes. The goal of pharmacological vitreolysis is to make the surgical intervention easier and less traumatic. METHODS: Different substances have been investigated, including chondroitinase, dispase, hyaluronidase, plasmin, and microplasmin. Besides preclinical investigations, hyaluronidase and microplasmin (ThromboGenics Ltd., Dublin, Leuven) have been tested clinically. Results from the literature are reported herein. RESULTS: Plasmin and microplasmin are both capable of inducing posterior vitreous detachment (PVD) in a dose- and time-dependent manner. There are no morphological or functional changes of the retina at therapeutic doses. Two phase II studies published to date demonstrate both efficacy and safety. Phase III studies are ongoing, and results are expected during 2010. Other enzymes tested show limitations in that retinal damage may occur (dispase) or liquefaction (hyaluronidase) occurs without cleavage of the vitreous cortex from the retina. CONCLUSIONS: Microplasmin induces PVD. Results from clinical trials show that microplasmin helps to detach the vitreous cortex from the retina. This may be advantageous in terms of complete vitreous removal and less traumatic intervention compared to mechanical techniques, such as vitrectomy and peeling of the internal limiting membrane.

[Volume calculations for current intravitreal injections of Lucentis]. / Volumenberechnungen zur aktuellen intravitrealen Injektion von Lucentis.

BACKGROUND: Medications for blocking vascular endothelial growth factor (VEGF) are currently used for therapy of neovascular age-related macular degeneration (AMD). Some users divide the original volume of the medication Lucentis into smaller aliquots to be used for several patients. The aim of this study was to investigate whether the current original aliquot volume of Lucentis can principally be subdivided to be used for treatment two patients each with a 0.05 ml injection volume. MATERIALS AND METHODS: The calculation of the dead space volume of the vessels used for injection was carried out by weighing the empty and full weights using an analytical balance. The sum of all dead space volumes was subtracted from the filling volumes. Additionally, the average extractable volume was determined from 200 original aliquots of Lucentis. RESULTS: Taking all necessary dead space volumes into consideration it was calculated that an extractable volume of at least 0.137 ml is necessary in order to be able to inject the necessary volume of 0.05 ml of the solution containing the active ingredient. The original volume of 0.23 ml contained in an aliquot of Lucentis cannot therefore be divided among two patients. The average extractable volume of 0.16 ml is clearly less than the full volume of 0.23 ml. CONCLUSIONS: The original aliquots of Lucentis contain a full volume of 0.23 ml and are not suitable to be used to treat two patients. The volume can only be divided among several patients if several original aliquots are pooled and refilled. This however, presupposes a renewed filling of aliquots which represents a new potential source of contamination. Also legal aspects and the question of stability of the active ingredient have not been taken into consideration.

[Retinal detachment in pediatrics : Etiology and risk factors]. / Ablatio retinae bei Kindern und Jugendlichen : Atiologie und Risikofaktoren.

BACKGROUND: Juvenile retinal detachment is uncommon but is a severe threat to visual acuity. This study demonstrates the etiology and risk factors of retinal detachment in patients age 0-20 years. PATIENTS AND METHODS: A cohort was selected comprising 259 patients (278 eyes) who were not older than 20 years at the age at onset of retinal detachment in the only or the first affected eye and had undergone surgery at least once at the Department of Ophthalmology of the University Medical Center of Munich between January 1980 and October 1998. This cohort was analyzed retrospectively with regard to medical antecedents. We separated the group consisting of only one affected eye or the first affected eye (259 eyes) from the group with bilateral retinal detachment (56 eyes). RESULTS: Of the 259 patients, 72% were male. The average age of onset was 13.5 years, and 27.8% suffered from a systemic disease in which malformations were frequent. The most frequent ocular antecedents were ocular trauma in 52.9% and ocular malformations, especially myopia in 37.5%. In 58.7% of the fellow eyes, there was a disorder predisposing to retinal detachment, and10.8% of the patients suffered from bilateral retinal detachment. The group with bilateral retinal detachment had a remarkably high percentage of systemic diseases as well as malformations that were most frequent in systemic and ocular antecedents. CONCLUSIONS: The study confirms ocular trauma and myopia as important risk factors for juvenile retinal detachment. Because of the high association with malformations as an endogenous background and their conspicuous frequency in patients with bilateral retinal detachment, a genetic background for retinal detachment may be concluded.

[Acute retinal necrosis]. / Akute Retinanekrose.

Acute retinal necrosis syndrome (ARN) is a rare retinitis caused by the herpes virus family, including herpes simplex virus and varicella zoster virus. ARN most commonly occurs in otherwise healthy patients of either sex at any age. It is characterized by an initial onset of episcleritis or scleritis, periorbital pain, and a frequently granulomatous anterior uveitis. The key criterion is a necrotizing retinitis starting in the periphery and spreading towards the posterior pole, associated with vitreous opacification. Optic neuropathy may also occur. A total of 75% of untreated eyes develop retinal detachment within the first two months after onset of the disease. Two out of three ARN cases show involvement of the fellow eye. Early intravenous antiviral therapy is mandatory to stop ARN progression. Peripheral retinal breaks can be treated by laser photocoagulation, thereby reducing the risk of retinal detachment. Vitreoretinal surgery is often required, and silicon oil is the tamponade of choice in ARN, resulting in good reattachment rates (90%). Visual prognosis, however, is guarded.

Interference microscopy delineates cellular proliferations on flat mounted internal limiting membrane specimens.

AIM: To demonstrate that interference microscopy of flat mounted internal limiting membrane specimens clearly delineates cellular proliferations at the vitreomacular interface. METHODS: ILM specimens harvested during vitrectomy were fixed in glutaraldehyde 0.05% and paraformaldehyde 2% for 24 h (pH 7.4). In addition to interference microscopy, immunocytochemistry using antibodies against glial fibrillar acidic protein (GFAP) and neurofilament (NF) was performed. After washing in phosphate-buffered saline 0.1 M, the specimens were flat-mounted on glass slides without sectioning, embedding or any other technique of conventional light microscopy. A cover slide and 4',6-diamidino-2-phenylindole (DAPI) medium were added to stain the cell nuclei. RESULTS: Interference microscopy clearly delineates cellular proliferations at the ILM. DAPI stained the cell nuclei. Areas of cellular proliferation can be easily distinguished from ILM areas without cells. Immunocytochemistry can be performed without changing the protocols used in conventional microscopy. CONCLUSION: Interference microscopy of flat mounted ILM specimens gives new insights into the distribution of cellular proliferations at the vitreomacular interface and allows for determination of the cell density at the ILM. Given that the entire ILM peeled is seen en face, the techniques described offer a more reliable method to investigate the vitreoretinal interface in terms of cellular distribution compared with conventional microscopy.

[Anti-VEGF treatment for retinal angiomatous proliferation]. / Intravitreale Anti-VEGF-Behandlung retinaler angiomatöser Proliferationen.

BACKGROUND: Retinal angiomatous proliferation (RAP) is a subform of neovascular age-related macular degeneration (AMD), which is characterized by a particularly poor prognosis. The aim of this study is to describe the loading phase and maintenance phase for RAP during intravitreal anti-VEGF treatment. MATERIAL AND METHODS: A total of 82 eyes in 82 patients with RAP stages 1-3 were treated during upload therapy with repeated intravitreal injections of 1.25 mg bevacizumab at intervals of 4 weeks until the retinal edema resolved. Baseline examination included measurement of the best corrected distance visual acuity (ETDRS chart), central retinal thickness using optical coherence tomography (OCT), and fluorescein angiography (FLA). During maintenance therapy, the patients' distance visual acuity was monitored at 4- to 12-week intervals and OCT or FLA performed if needed. The average follow-up was 7.4 months (SD 4.2). Treatment with intravitreal anti-VEGF therapy was repeated if there was evidence of sub- or intraretinal fluid with a decrease in visual acuity of 5 points or more, increase of the central retinal thickness of 100 microm or more on OCT, or subjective deterioration with verifiable sub- or intraretinal fluid. RESULTS: During upload therapy an improvement in visual acuity of an average of +5.1 letters (mean, n=82 eyes) was observed. During maintenance therapy it was initially possible to sustain this treatment effect. However, 5 months after loading therapy was concluded, a deterioration of -5.5 letters (mean, n=31) was evident in comparison with the end of loading therapy. During the further course deterioration continued (12-month follow-up: -8.6 letters, n=7). Recurrence occurred in 60% of the cases, on average 8 weeks after termination of loading therapy. During an observation period of 6 months (n=66) a total of 3.6 injections were necessary. CONCLUSIONS: Therapy with intravitreal anti-VEGF medications represents a treatment option for RAP, but in the long term the disease continues to progress accompanied by functional deterioration. We thus recommend that patients with RAP be monitored at 4-week intervals to permit early treatment of recurrence.

Enzymatic vitreous disruption.

Enzymatic vitreous disruption refers to cleaving the vitreoretinal junction by enzymatic means, thereby inducing posterior vitreous detachment (PVD) and liquefaction of the vitreous gel. Several enzymes have been proposed in this respect, including chondroitinase, hyaluronidase, dispase, and plasmin. In an experimental setting, chondroitinase induced PVD and was helpful in removing epiretinal membranes but no further data have been reported yet. Hyaluronidase liquefies the vitreous as demonstrated in a phase III trial in diabetic patients with vitreous haemorrhage. Dispase induces PVD but also causes inner retinal damage and is now used as an animal model of proliferative vitreoretinopathy. Plasmin has the capability of both PVD induction and liquefaction. However, plasmin is highly unstable and not available for clinical use. Microplasmin (ThromboGenics Ltd, Dublin, Ireland) is a truncated form of human plasmin sharing the same catalytic activity like plasmin. Recombinant microplasmin is under clinical investigation in patients with vitreomacular traction. This review article reports on the current knowledge of enzymatic vitreous disruption and discusses details of the enzyme candidates in basic and clinical research terms.

[Possible role of alkylphosphocholines in retinal reattachment surgery]. / Mögliche rolle von alkylphosphocholinen bei der ablatio-chirurgie.

BACKGROUND: Proliferative vitreoretinopathy (PVR) is a major complication after retinal detachment surgery, but there is no established pharmacotherapy available to control the cell biology of the disease. The aim of this study was to investigate the role of alkylphosphocholines [APCs; erucylphosphocholine (ErPC) was used in this study], novel pharmacologic substances with antiproliferative properties, on intraretinal proliferation initiated by experimental retinal detachment in a well-established in vivo model. METHODS: Retinal detachments were created in adult pigmented rabbits. ErPC was injected intravitreally on either day 1 or day 2 after detachment. Bromodeoxyuridine (5-bromo-2-deoxyuridine, BrdU) was injected on day 3. Following fixation, retinas were triple-labelled with anti-BrdU (proliferation marker), Isolectin B4 (retinal microglia marker), and anti-vimentin (retinal Mueller glia cell marker). The number of anti-BrdU-labelled cells per millimeter of retina was determined from sections imaged by laser scanning confocal microscopy. Toxicity was assessed by light and electron microscopy. RESULTS: A single intravitreal injection of ErPC had a significant effect on reducing the number of proliferating non-neural retinal cells on day 3 after experimental retinal detachment in the rabbit. Injection of ErPC on day 1 was more effective than when given on day 2. No evidence of toxicity was observed in the retina on day 3 for any of the conditions. CONCLUSIONS: APCs are novel pharmacologic substances that significantly inhibited intraretinal proliferation after experimental retinal detachment in this in vivo model. They could be considered as an adjunct therapy at the time of retinal reattachment surgery to potentially prevent proliferative vitreoretinal diseases such as PVR. However, long-term toxicity studies must be performed before APCs can be considered for clinical application.

[The primary objective in macular hole surgery. Ultrastructural features of the vitreomacular interface]. / Operative Zielvorgabe in der Makulaforamenchirurgie. Neue Aspekte zur Feinstruktur der vitreomakulären Grenzfläche.

We compared the ultrastructure of the inner limiting membrane (ILM) and epiretinal tissue in closed and non-closed, idiopathic macular holes (MH). Peeling of ILM and epimacular tissue during vitrectomy was successfully performed on 77 eyes with stage III MH and on 19 eyes with stage IV MH. In 16 additional eyes with non-closed MH, we performed a second vitrectomy with extended ILM removal. The specimens were processed for transmission electron microscopy. Fibrocellular proliferation at the vitreal side of the ILM was found in 57% of MH that were closed by one operation, and in 100% of non-closed MH. Mono- and multilayered cellular membranes as well as native vitreous collagen at the ILM were significantly more frequent in eyes with stage IV MH than in eyes with stage III MH. In non-closed MH, cellular proliferation was mostly seen as irregular cell accumulation, and masses of newly formed collagen were found. Since ILM remnants and collagen represent a stimulus for the early formation of tangential traction preventing successful MH closure, it appears mandatory to create a complete vitreoretinal separation and to remove the ILM and collagen thoroughly during MH surgery.

[The need for pharmacology in vitreoretinal surgery SOE Lecture 2007]. / Die Kombination von Pharmakologie und Vitrektomie kann die Grenzen der mechanischen vitreoretinalen Chirurgie überwinden.

BACKGROUND: While the limits of mechanical vitrectomy are being approached, scientists and vitreoretinal surgeons are looking for a combination of pharmacology and vitrectomy, i. e., pharmacology-assisted vitrectomy. METHODS: This review shows the limits of conventional vitreoretinal surgery by presenting clinical and ultrastructural data related to vitreoretinal surgical techniques and outcomes. RESULTS: The limits of conventional vitreoretinal surgery include: 1. Incomplete vitreous cortex removal. 2. Surgery of advanced stages of the disease. 3. The lack of neuroprotection and antiproliferative agents. 4. Ill-defined cleavage planes when removing tissue from the retina. CONCLUSIONS: Pharmacology-assisted vitrectomy helps to overcome the limits of conventional vitreoretinal surgery by addressing: Item 1. Pharmacological vitreolysis. Item 2. Earlier, less traumatic intervention. Item 3. Neuroprotection and antiproliferative agents. Item 4. Selective staining of distinct structures of the vitreoretinal interface, such as cortical vitreous, cellular proliferation, and internal limiting membrane.

[Diagnostic and therapeutic options in diabetic retinopathy]. / Diagnostik und Therapie der diabetischen Retinopathie Schicken Sie lhre Diabetiker regelmässig zur Fundoskopie.

Diabetes mellitus is the systemic disease that most often leads to blindness. Since the diminishment of visual acuity is a late symptom of the disease, screening examinations are of particular importance, as only in this way can the optimal time point for treatment be determined. Stage-oriented laser therapy prevents blindness due to macular edema or proliferative diabetic retinopathy. For a number of years, vitreoretinal surgery has enabled the treatment of late ocular manifestations such as bleeding into the vitreous body and traction retinal detachment. With appropriate stage-oriented treatment, hopeless cases of diabetic retinopathy ending in blindness should become the exception. The only useful and confirmed effective medical treatment capable of delaying this late complication continues to be careful blood glucose and blood pressure control.

[Surgical treatment of cataract]. / Raten Sie zur OP, damit die Welt wieder bunt wird.

Today, the most frequently performed of all operative interventions is considered to be surgery for cataract. Modern surgical techniques applied under local anesthesia, tiny incisions that close spontaneously, reliable biometric methods, and the availability of artificial lenses, all combine to produce excellent results. In view of the low complication rate, this procedure can be recommended even in very old patients.

[Circulatory disorders of the retina]. / Probleme mit den Augen - Fehler im System?

Cardiovascular diseases lead to systemic vascular regression, which, among other consequences, may result in an impairment of retinal perfusion. In view of the high level of comorbidity observed in patients with circulatory problems affecting the retina, the early recognition of mild forms of vascular retinopathy is of considerable importance. A major prerequisite for an improvement in outcome is the recognition of the fact that most circulatory disorders of the retina are due to systemic vascular disease, and the eye is an important prognostic indicator of cardiovascular morbidity and mortality. As a result, effective communication between family physician/internist and ophthalmologist is basic to the successful treatment of these diseases of the eye.

[Age-related macular degeneration]. / Zur Prophylaxe: Spinat, ein Vitaminpräparat und Zink

In the western world, macular degeneration is the most common cause of severe loss of vision and blindness in persons older than 50. The underlying cause of the condition is a disturbance in the interaction between the retina and choroid of the macula. Apart from age itself, genetic disposition and smoking are confirmed risk factors. In the initial stages, the patient experiences merely a mild blurring of vision. The wet form, which is usually progressive, is experienced as an acute loss of vision or distortion of the objects viewed. Underlying this wet macular degeneration is of new vessel growth from the choroid, known as choroidal neovascularization, which as a result of exudation of fluid and bleeding into the macula, destroys central vision. Apart from the administration of vitamins to slow down progression, laser coagulation, photodynamic treatment or vitreoretinal surgery may be helpful in some cases. A specific causal therapy is, however, not available.

Ultrastructure of vitreomacular traction syndrome associated with persistent hyaloid artery.

AIM: To demonstrate the ultrastructure of vitreomacular traction associated with persistent hyaloid artery. METHODS: Pars plana vitrectomy was performed in a 66-year-old man with progressive vitreomacular traction associated with a persistent hyaloid artery. Epimacular tissue was peeled and processed for transmission electron microscopy. RESULTS: Ultrastructural analysis revealed multiple sheets of cellular and collagenous components. Myofibroblasts and newly formed collagen were the predominant features. Fibrous astrocytes, fibroblasts, macrophages, and basement membrane were also present. CONCLUSION: The cellular composition of the epimacular tissue and high cellular activity suggest that persistence of the hyaloid artery may contribute to the development of vitreomacular traction.