Karl Ulrich Bartz-Schmidt

Polypoidal choroidal vasculopathy pattern in age-related macular degeneration - A clinicopathologic correlation.

Purpose: To report the histopathologic features of surgically removed submacular tissue from an elderly patient with a pattern of polypoidal choroidal vasculopathy on indocyanine green angiography. Methods: Clinical examination including fluorescein and indocyanine green angiography and light microscopy of surgical specimen. Results: A thick yellow proteinaceous subretinal fluid was seen in the right macula of an 81‐year‐old white man. Fluorescein angiography indicated progressive leakage from undetermined source apart from a few focal hyperfluorescent points. Indocyanine green angiography showed several polyps as well as dilated choroidal vessels in the macula and along the superior temporal arcade. A large plaque was visualized in the late phase. Microscopically, the specimen consisted of a thick fibrovascular membrane located on the choroidal side of the retinal pigment epithelium (RPE). The RPE layer was discontinuous whereas on its choroidal side an almost intact layer of diffuse drusen was observed. A group of dilated thin‐walled vessels were found that appeared to be saccular on serial sections. Some of these were located almost immediately under the diffuse drusen. Conclusion: Histologic examination of submacular tissue removed from an eye with polypoidal choroidal vasculopathy showed several aneurysmal dilatations located directly under diffuse drusen within a sub‐RPE, intra‐Bruchs fibrovascular membrane.

Subretinally transplanted embryonic stem cells rescue photoreceptor cells from degeneration in the RCS rats.

The Royal College of Surgeons (RCS) rat is an animal model for retinal degeneration such as the age-related macular degeneration. The RCS rat undergoes a progressive retinal degeneration during the early postnatal period. A potential treatment to prevent this retinal degeneration is the transplantation into the subretinal space of cells that would replace functions of the degenerating retinal pigment epithelium (RPE) cells or may form neurotrophic factors. In this study we have investigated the potential of subretinally transplanted embryonic stem cells to prevent the genetically determined photoreceptor cell degeneration in the RCS rat. Embryonic stem cells from the inner cell mass of the mouse blastocyst were allowed to differentiate to neural precursor cells in vitro and were then transplanted into the subretinal space of 20-day-old RCS rats. Transplanted and sham-operated rats were sacrificed 2 months following cell transplantation. The eyes were enucleated and photoreceptor degeneration was quantified by analyzing and determining the thickness of the outer nuclear layer by light and electron microscopy. In the eyes transplanted with embryonic cells up to 8 rows of photoreceptor cell nuclei were observed, whereas in nontreated control eyes the outer nuclear layer had degenerated completely. Transplantation of embryonic stem cells appears to delay photoreceptor cell degeneration in RCS rats.

Clinicopathological correlation in exudative age related macular degeneration: histological differentiation between classic and occult choroidal neovascularisation.

AIMS To analyse the histopathology of classic and occult choroidal neovascular membrane surgical specimens in age related macular degeneration. METHODS 35 membranes, from a consecutive series of surgically removed choroidal neovascular membranes in age related macular degeneration, were classified as classic or occult following the guidelines of the Macular Photocoagulation Study. Membranes with classic as well as occult components were considered as mixed membranes. The membranes were serially sectioned and stained with haematoxylin and eosin, Masson trichrome, periodic acid-Schiff, and phosphotungstic acid haematoxylin stain. The correlation has been made in a masked fashion. RESULTS 31 membranes (19 classic, 10 occult, and two mixed membranes) could be analysed histologically. 18 classic choroidal neovascular membranes had a major subretinal fibrovascular component and 10 of these had an additional, minor fibrovascular component under the retinal pigment epithelium. The 10 occult membranes contained a fibrovascular component under the retinal pigment epithelium and the two mixed membranes contained fibrovascular tissue on both sides of the retinal pigment epithelium. Fibrin and remains of outer segments tended to occur at the lateral edges of classic membranes and to cover the inner surface of occult membranes. CONCLUSION Classic choroidal neovascularisation in age related macular degeneration is predominantly composed of subretinal fibrovascular tissue while occult choroidal neovascularisation is composed of fibrovascular tissue at the choroidal side of the retinal pigment epithelium.

Primary vitrectomy for pseudophakic retinal detachment.

AIM/BACKGROUND: Viewing the peripheral retina is the major problem in the repair of pseudophakic retinal detachments. Conventional buckling procedures in pseudophakic eyes are complicated by persistent retinal (re-) detachment and proliferative vitreoretinopathy (PVR) more often than in phakic eyes. METHODS: Primary vitrectomy was performed in 33 consecutive cases for pseudophakic retinal detachment with the help of liquid perfluorocarbons and a wide angle viewing system, following a standardised procedure. All eyes have passed the 12 month follow up examination. RESULTS: The primary reattachment rate was 94%. PVR was observed in one case (3%). Seventy nine per cent (26 eyes) regained vision of 20/50 or better, with a median visual acuity of 20/30. The most frequent complication was transient glaucoma during the early postoperative period in 48% (16 eyes) requiring carboanhydrase inhibitors. CONCLUSION: The main advantage of primary vitrectomy over conventional buckling seems to be the better intraoperative sight to the most peripheral retinal holes, controlled removal of vitreous traction, and focused endolaser coagulation. This may explain the low rate of PVR after primary vitrectomy. Also, visual results tended to be better compared with conventional surgical techniques possibly because of removed vitreous opacities, and because of a superior retinal reattachment rate as well as the reduced rate of PVR.

Extraocular surgery for implantation of an active subretinal visual prosthesis with external connections: feasibility and outcome in seven patients

Background: Due to low energy levels in microphotodiode-based subretinal visual prostheses, an external power supply is mandatory. We report on the surgical feasibility and the functional outcome of the extraocular part of an approach to connect a subretinal prosthesis to an extracorporeal connector in the retro-auricular space via a trans-scleral, transchoroidal cable. Methods: Seven volunteers with retinitis pigmentosa received an active subretinal implant; energy was supplied by gold wires on a trans-sclerally, transchoroidally implanted polyimide foil leading to the lateral orbital rim where it was fixated and connected to a silicone cable. The cable was implanted subperiostally beneath the temporal muscle using a trocar to the retro-auricular space where it penetrated the skin for connection to a stimulator. To avoid subretinal movement of the implant, three tension relief points have been introduced. Results: All implantations were performed as planned without complications, and no serious adverse events occurred in the postoperative period. Fixation of the implants was stable throughout the entire study duration of 4 weeks; permanent skin penetration proved to be uncomplicated. Motility was minimally restricted in downgaze and ab-/adduction. Explantation was uneventful. Conclusion: The above-described procedure provides a method for stable fixation of a subretinal device with a trans-scleral, transchoroidal cable connection to an extracorporeal connector.

Transcorneal Electrical Stimulation for Patients with Retinitis Pigmentosa: A Prospective, Randomized, Sham-Controlled Exploratory Study

PURPOSE To assess the safety of transcorneal electrical stimulation (TES) and explore its efficacy in various subjective and objective parameters of visual function in patients with retinitis pigmentosa (RP). METHODS Twenty-four patients in this prospective, randomized, partially blinded, good-clinical-practice study underwent TES (5-ms biphasic pulses; 20 Hz; DTL electrodes) 30 minutes per week for 6 consecutive weeks. The patients were randomly assigned to one of three groups: sham, 66%, or 150% of individual electrical phosphene threshold (EPT). Visual acuity (VA), visual field (VF; kinetic, static), electroretinography (Ganzfeld, multifocal), dark-adaptation (DA), color discrimination, and EPTs were assessed at all visits or four times, according to the study plan. RESULTS TES using DTL electrodes was tolerated well; all patients finished the study. Two adverse (foreign body sensation), but no serious adverse events were encountered. There was a tendency for most functional parameters to improve (8/18) or to remain constant (8/18) in the 150% group. VF area and scotopic b-wave amplitude reached statistical significance (P < 0.027 and P < 0.001, respectively). Only desaturated color discrimination and VF mean sensitivity decreased. There was no obvious trend in the 66% group. CONCLUSIONS TES was found to be safe in RP patients. Positive trends were discovered, but due to the small sample size of this exploratory study, statistical significance was reached only for VF area and scotopic b-wave amplitude. Further studies with larger sample sizes and longer duration are needed to confirm the findings and to define optimal stimulation parameters. (ClinicalTrials.gov number, NCT00804102.).

Clinicopathological correlation of deep retinal vascular anomalous complex in age related macular degeneration

AIMS To analyse the histopathology of “deep retinal vascular anomalous complex” or “chorioretinal anastomosis”. METHODS Six patients with a deep retinal vascular anomalous complex (age range 66–88 years) had fundus photography and fluorescein angiography not more than 14 days before foveal translocation surgery. Four patients were also documented with indocyanine green angiography. The surgical specimens were serially sectioned and stained in a stepped fashion with Masson trichrome, periodic acid Schiff, and phosphotungstic acid haematoxylin, a histochemical stain for fibrin. RESULTS A subretinal fibrovascular membrane was surrounded by a rim consisting of diffuse drusen (basal laminar deposits), retinal pigment epithelium, and amorphous, fibrinous material interspersed with remains of outer segments in all specimens. In two specimens vascular structures were identified that left the specimen towards the retina. Amorphous material with the remains of outer segments was not found on the retinal side of the fibrovascular tissue itself but in four specimens a small neuroretinal portion (outer nuclear layer) was adherent to the complex. In three specimens a thin fibrocellular membrane was seen at the choroidal side of the diffuse drusen. CONCLUSION Deep retinal vascular anomalous complex represents histologically neovascularisation growing out of the neuroretina, into the subretinal space, which mimics choroidal neovascularisation. The term therefore appears rightly chosen.

Scleral buckling versus primary vitrectomy in rhegmatogenous retinal detachment (SPR Study) : design issues and implications: SPR Study Report No. 1

Abstract.Background: In patients with more complex rhegmatogenous retinal detachments (RRD) not complicated by proliferative vitreoretinopathy (PVR), the most appropriate operating method is controversial, and different surgeons use different techniques. The Scleral Buckling Versus Primary Vitrectomy in Rhegmatogenous Retinal Detachments Study (SPR Study) is designed to compare primary vitrectomy and scleral buckling techniques in these patients. Methods: The SPR Study is a multicentre, randomised, controlled clinical trial stratified by lens status. Patients with RRD which is not complicated by PVR grade B or C and which cannot be treated with a single meridional sponge are randomised to either scleral buckling or pars plana vitrectomy as first surgical intervention. Four hundred consecutive patients are to be recruited per subtrial (phakic and aphakic/pseudophakic patients), and followed up for 1 year. The primary endpoint (functional outcome) is the change in visual acuity. Secondary endpoints (anatomical outcome) include postoperative PVR, retinal reattachment and the number of reoperations necessary to achieve retinal reattachment. Twenty-seven institutions (49 surgeons) in six European countries have been recruited for participation in the study. Conclusion: The SPR Study is the first randomised prospective clinical trial to compare scleral buckling and primary vitrectomy in patients with RRD. The results of this study should enable vitreoretinal surgeons to improve the surgical therapy of patients with the more complicated manifestations of RRD.

Nebenwirkungen und Komplikationen der intravitrealen Triamcinolonacetonid-Therapie

ZusammenfassungMit der Etablierung der intravitrealen Injektion von Triamcinolonacetonid (TA) in der klinischen Routine wird auch das Bewusstsein um mögliche Nebenwirkungen geschärft. Dabei wird die Diskussion durch die potenzielle Toxizität einzelner biounverträglicher Inhaltsstoffe beherrscht. Diese werden als wesentlicher pathogenetischer Faktor der sterilen Pseudoendophthalmitis angesehen, die jedoch durch die Aufreinigung kommerzieller Präparate weitgehend überwunden scheint. Auch sub- oder epiretinale Ablagerungen zeigen klinisch keinen Anhalt für eine retinale Toxizität.Relevante Nebenwirkungen umfassen insbesondere das temporäre Kortikosteroidglaukom und die Progredienz einer vorbestehenden Katarakt. Als seltene, aber schwerwiegende Komplikation gilt die bakterielle Endophthalmitis, die im Zusammenhang mit dem angewandten Hygienestandard kritisch betrachtet werden muss. Sie kann durch die steroidinduzierte Immunsuppression klinisch maskiert sein. Als seltenere Komplikationen sind ein transienter Zentralarterienverschluss, konjunktivale Ulzerationen, eine Ablatio sowie möglicherweise die Reaktivierung einer Zytomegalievirusretinitis beschrieben.Insgesamt sind die Komplikationen und Nebenwirkungen in ihrem Spektrum und den zugrunde liegenden Pathomechanismen zwar vielfältig, erscheinen in ihren Auswirkungen jedoch zumeist passager und gut beherrschbar.AbstractWith the advent of intravitreal triamcinolone acetonid injections major focus was assigned to potential ocular side effects. The current discussion is dominated by the potential cytotoxicity of particular biologically incompatible components. Those are regarded as substantial pathogenetic factor of the sterile pseudoendophthalmitis that seems to be avoidable by meticulous purification of the commercially available preparations. Even sustained subretinal or epiretinal deposits disclosed no signs of retinal toxicity.Major ocular side effects comprise temporary corticosteroid glaucoma and progressive cataract formation. Infectious endophthalmitis represents a rare but serious complication that might be set into critical context with hygienic surgical standards applied. Due to steroid-induced immune suppression clinical signs of inflammation might be masked and a proper diagnosis delayed. Other rare complications reported include a transient central retinal artery occlusion, conjunctival ulcerations, retinal detachment and potential reactivation of a cytomegalovirus retinitis.In conclusion, ocular side effects and complications show a wide variety of clinical signs and underlying causal mechanisms. However, the consequences are mostly temporary and show a good response to therapeutic intervention.

Phagocytosis of rod outer segments by human iris pigment epithelial cells in vitro.

Abstract · Background: We set out to evaluate the growth potential of human iris pigment epithelial (hIPE) cells in vitro, to establish whether these cells acquire the ability to phagocytose rod outer sgments (ROS) and to compare the phagocytic activity of hIPE to that of human retinal pigment epithelial (hRPE) cells. · Methods: hIPE and hRPE cells were isolated and cultured from human donor eyes and surgical specimens and growth characteristics were analyzed. HIPE and hRPE of an eye of a 46-year-old donor were used for the phagocytosis assay. Phagocytosis was evaluated by adding ROS isolated from porcine retina to cultures of hIPE and hRPE, which had been labeled with the pH-sensitive fluorescent dye, carboxy-SNAFL. After 4 h the number of ingested ROS was counted with a light microscope. For each cell type phagosomes in 500 cells were counted. The epithelial characteristics of the cells used in this study were evidenced by their morphology. · Results: Morphologically cultured hIPE are indistinguishable from the hRPE cultured from the same donor eye and show a similar pattern of cytokeratin distribution. Cultured hIPE acquire the ability to phagocytose ROS at a level slightly lower than hRPE; hIPE contained 0.76 phagosomes per cell, hRPE 0.99 phagosomes per cell. · Conclusion: The morphology of hIPE in culture and the acquisition of the phagocytic phenotype indicate that these cells have the ability to differentiate into cells that have characteristics in common with hRPE. The acquisition of phagocytic activity suggests that it is feasible to culture hIPE from surgical iridectomies and that these cultured cells can be transplanted into the subretinal space in individuals with retinal degenerations.