How to prove neglect in the context of the post-mortem examination.

Understanding the causes, extent, and period of neglect is not only a medical but also a forensic task when it comes to legal investigations. In this study, we evaluated 46 autopsied cases where there was clear evidence of physical neglect during the last period of the deceased's life. The age of the deceased ranged from 21 to 96 years; most of them were female (71.7%). The majority of cases (89.9%) took place in a domestic environment, with partners or relatives providing care. The most frequent post-mortem findings were pressure sores, followed by inflammatory skin changes, and signs of malnutrition and dehydration. Neglect was the cause or co-cause of death in 23% of the cases. More than half of the deceased showed severe contamination of the skin surface by excrement, and in almost 40% of the cases, fly infestation was found. The majority of insects belonged to the group of house flies (Diptera: Muscidae), mainly the common house fly, Musca domestica. By analyzing the entomological evidence, it was possible to prove an insect infestation period of at least several days ante-mortem. Since the period of neglect may be relevant in terms of legal proceedings, the present work demonstrates the particular importance of insect traces in providing this evidence. While prosecution and conviction of caregivers remain challenging, it is all the more essential that entomology and legal medicine collaborate on the analysis of findings of neglect.

[Barrett's esophagus and carcinoma: Recommendations of the S2k guideline 2014 and the S3 guideline 2015]. / Barrett-Ösophagus und Barrett-Karzinom: Empfehlungen gemäß S2k­Leitlinie von 2014 und S3­Leitlinie von 2015.

In the current S2k guideline for gastroesophageal reflux disease and the new S3 guideline for esophageal cancer, histopathological evaluation of Barrett's esophagus has been revised and supplemented. The histological diagnosis of Barrett's esophagus still requires the proof of a specialized intestinal metaplastic epithelium (columnar epithelium with goblet cells). Barrett mucosa must be classified as negative, unclear/doubtful, and positive concerning the intraepithelial neoplasia (IEN)/dysplasia according to the current WHO guideline. Each IEN should be confirmed by an external second opinion due to poor interobserver variability. The pathological classification is of decisive importance here, since the recommended monitoring intervals are based solely on the ground of proved IEN. Risk factors in endoscopic resection specimens such as depth of infiltration (m1-m4; sm1-sm3; distance in µm); angioinvasion (L, V); grading and lateral/basal resection margin have to be reported. In surgical specimens, the reference of the tumor center to the gastroesophageal junction and in the neoadjuvant situation the tumor regression should be documented.

Fibroblast activation protein-α, a stromal cell surface protease, shapes key features of cancer associated fibroblasts through proteome and degradome alterations.

Cancer associated fibroblasts (CAFs) constitute an abundant stromal component of most solid tumors. Fibroblast activation protein (FAP) α is a cell surface protease that is expressed by CAFs. We corroborate this expression profile by immunohistochemical analysis of colorectal cancer specimens. To better understand the tumor-contextual role of FAPα, we investigate how FAPα shapes functional and proteomic features of CAFs using loss- and gain-of function cellular model systems. FAPα activity has a strong impact on the secreted CAF proteome ("secretome"), including reduced levels of anti-angiogenic factors, elevated levels of transforming growth factor (TGF) ß, and an impact on matrix processing enzymes. Functionally, FAPα mildly induces sprout formation by human umbilical vein endothelial cells. Moreover, loss of FAPα leads to a more epithelial cellular phenotype and this effect was rescued by exogenous application of TGFß. In collagen contraction assays, FAPα induced a more contractile cellular phenotype. To characterize the proteolytic profile of FAPα, we investigated its specificity with proteome-derived peptide libraries and corroborated its preference for cleavage carboxy-terminal to proline residues. By "terminal amine labeling of substrates" (TAILS) we explored FAPα-dependent cleavage events. Although FAPα acts predominantly as an amino-dipeptidase, putative FAPα cleavage sites in collagens are present throughout the entire protein length. In contrast, putative FAPα cleavage sites in non-collagenous proteins cluster at the amino-terminus. The degradomic study highlights cell-contextual proteolysis by FAPα with distinct positional profiles. Generally, our findings link FAPα to key aspects of CAF biology and attribute an important role in tumor-stroma interaction to FAPα.

Increased expression of angiogenic and inflammatory proteins in the vitreous of patients with ischemic central retinal vein occlusion.

BACKGROUND: Central retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO. METHODS: Vitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray. RESULTS: Expression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE). CONCLUSION: Proteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach.

Choroidal neovascularization reduced by targeted drug delivery with cationic liposome-encapsulated paclitaxel or targeted photodynamic therapy with verteporfin encapsulated in cationic liposomes.

PURPOSE: Intravitreal antivascular endothelial growth factor (anti-VEGF) application has revolutionized the treatment of choroidal neovascularization (CNV), a hallmark of wet age-related macular degeneration. However, additional treatment options are desirable as not all CNV lesions respond to anti-VEGF injections. Here, we assessed the feasibility of targeted delivery of cationic liposome-encapsulated paclitaxel (EndoTAG-1) in treating CNV. Furthermore, we investigated whether a new formulation of verteporfin encapsulated in cationic liposomes (CL-VTP) enhances the effect of photodynamic therapy (PDT). METHODS: EndoTAG-1, LipoSPA, and CL-VTP were produced by encapsulating paclitaxel, succinyl-paclitaxel, or verteporfin in cationic liposomes (CL). Mice underwent argon laser coagulations at day 0 (D0) to induce CNV. EndoTAG-1 and LipoSPA were injected into the tail vein at D1, D3, D5, D7, and D9. Taxol, CL, or trehalose buffer alone was injected in control animals. At D10, all animals were perfused with fluorescein isothiocyanate (FITC)-dextran. Flatmounts comprising the retinal pigment epithelium, choroid, and sclera were prepared for quantifying the CNV by measuring the area of lesions perfused with FITC-dextran. For PDT, mice received an injection with CL-VTP or Visudyne at D10. One eye was treated with PDT while the other served as a control. Evaluation of RPE-choroid-scleral and retinal flatmounts was performed at D12, D14, or D17. Perfusion with FITC-dextran and tetramethylrhodamine-5-(and 6)-isothiocyanate-lectin staining was used to distinguish between perfused and non-perfused choroidal vessels. RESULTS: EndoTAG-1 or LipoSPA significantly reduced CNV size to 15% compared to trehalose controls. The mean CNV area of mice treated with CL was reduced (though not significantly) to about one-half of the value of the trehalose control group. The same was observed for paclitaxel. Thus, the reduction in the CNV size between treatment with CL and treatment with EndoTAG-1 or LipoSPA was 40%, which was not significant. PDT using either CL-VTP or Visudyne reduced CNV size to 65% (D17) of trehalose control size. CNV size was further diminished to 56% with Visudyne and 53% with CL-VTP when PDT was repeated twice. Most importantly, PDT-associated retinal damage was less pronounced using CL-VTP compared to Visudyne. CONCLUSIONS: Systemic intravenous injection of paclitaxel (EndoTAG-1)- or succinyl-paclitaxel (LipoSPA)-loaded CL had a significant antiangiogenic effect in a CNV mouse model. PDT with CL-VTP was as effective as Visudyne in neovascular obliteration but induced less tissue damage. Our data suggest that systemic application of cationic liposome formulations may serve to treat ocular neovascular diseases. This approach may reduce the need for intraocular injections and may benefit patients with neovascular lesions irresponsive to anti-VEGF treatment.

In vivo imaging of choroidal angiogenesis using fluorescence-labeled cationic liposomes.

PURPOSE: Precise monitoring of active angiogenesis in neovascular eye diseases such as age-related macular degeneration (AMD) enables sensitive use of antiangiogenic drugs and reduces adverse side effects. So far, no in vivo imaging methods are available to specifically label active angiogenesis. Here, we report such a technique using fluorophore-labeled cationic liposomes (CL) detected with a standard clinical in vivo scanning laser ophthalmoscope (SLO). METHODS: C57Bl/6 mice underwent laser coagulations at day 0 (d0) to induce choroidal neovascularization (CNV). Liposomes labeled with Oregon green, rhodamine (Rh), or indocyanine green (ICG) were injected into the tail vein at various time points after laser coagulation, and their fluorescence was observed in vivo 60 min later using an SLO, or afterwards in choroidal flatmounts or cryosections. RESULTS: SLO detected accumulated fluorescence only in active CNV lesions with insignificant background noise. The best signal was obtained with CL-ICG. Choroidal flatmounts and cryosections of the eye confirmed the location of retained CL in CNV lesions. Neutral liposomes, in contrast, showed no accumulation. CONCLUSIONS: These results establish fluorophore-labeled CL as high affinity markers to selectively stain active CNV. This novel, non-invasive SLO imaging technique could improve risk assessment and indication for current intraocular antiangiogenic drugs in neovascular eye diseases, as well as monitor therapeutic outcomes. Labeling of angiogenic vessels using CL can be of interest not only for functional imaging in ophthalmology but also for other conditions where localization of active angiogenesis is desirable.

Levels of VEGF but not VEGF(165b) are increased in the vitreous of patients with retinal vein occlusion.

PURPOSE: To determine the concentration of the pro-angiogenic vascular endothelial growth factor VEGF(165) (VEGF) and the anti-angiogenic VEGF(165b) in vitreous samples of patients with branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) in comparison to patients without retinal occlusive disease. DESIGN: Experimental laboratory investigation. METHODS: Vitreous samples were collected from patients undergoing surgery for arteriovenous dissection after BRVO, radial optic neurotomy after CRVO in the occlusion group, or macular pucker or macular hole in the control group. Concentrations of VEGF and VEGF(165b) were determined by ELISA and an ELISA-type antibody microarray. RESULTS: Average vitreal concentration of VEGF was 8.6 ng/mL in the CRVO group and 2.0 ng/mL in the BRVO group as compared to 0.26 ng/mL in the control group. Average vitreal concentration of VEGF(165b) was 27 pg/mL in the CRVO group, 42 pg/mL in the BRVO group, and 49 pg/mL in the control group. In patients with CRVO and BRVO, the angiogenic balance was shifted towards angiogenic stimulation. CONCLUSION: The severity of RVO from BRVO to CRVO correlates with an increase of VEGF and the decrease of VEGF(165b), indicating a pro-angiogenic shift. Altering the ratio of VEGF(165b)/VEGF(165) might be a feasible approach for treating retinal occlusive diseases.

Intravitreal bevacizumab (Avastin) versus ranibizumab (Lucentis) for the treatment of age-related macular degeneration: a safety review.

AIM: To conduct a systematic review in order to compare adverse effects (AE) and the reporting of harm in randomised controlled trials (RCTs) and non-RCTs evaluating intravitreal ranibizumab and bevacizumab in age-related macular degeneration. METHODS: Medline, Embase and the Cochrane Library were searched with no limitations of language and year of publication. Studies which compared bevacizumab or ranibizumab as monotherapy with any other control group were included. Case series were included if they met predefined quality standards. RESULTS: The 2 year results of phase III trials evaluating ranibizumab show that the rates of serious ocular AE were low (≤2.1%) but indicate major safety concerns (RR 3.13, 95% CI 1.10 to 8.92). A possible signal with regard to thromboembolic events (RR 1.35, 95% CI 0.66 to 2.77) and a significant increase in non-ocular haemorrhage (RR 1.62, 95% CI 1.03 to 2.55) were also noted. In contrast to ranibizumab trials, the RCTs evaluating bevacizumab are of limited value. The main shortcomings are small sample sizes and an apparent lack of rigorous monitoring for AE. A critical assessment of the large number of published case series evaluating bevacizumab also shows that no reliable conclusions on safety can be drawn using this study design. Therefore, any perception that intravitreal bevacizumab injections are not associated with major ocular or systemic AE are not supported by reliable data. CONCLUSION: The bevacizumab studies show too many methodological limitations to rule out any major safety concerns. Higher evidence from ranibizumab trials suggests signals for an increased ocular and systemic vascular and haemorrhagic risk which warrants further investigation.

Therapeutic interference with EphrinB2 signalling inhibits oxygen-induced angioproliferative retinopathy.

PURPOSE: To investigate whether EphrinB2 (EfnB2) or EphB4 influence retinal angiogenesis under physiological or pathological conditions. METHODS: Using the mouse model of oxygen-induced proliferative retinopathy (OIR), the expression of EfnB2, EphB4, vascular endothelial growth factor (VEGF), VEGFR1 and VEGFR2 was quantified by quantitative polymerase chain reaction (qPCR) and localized in EfnB2- and EphB4-lacZ mice. Angioproliferative retinopathy was manipulated by intravitreal injection of dimeric EfnB2 and monomeric or dimeric EphB4. RESULTS: Dimeric EphB4 (EphB4-Fc) and EfnB2 (EfnB2-Fc) enhanced hypoxia-induced angioproliferative retinopathy but not physiological angiogenesis. Monomeric EphB4 (sEphB4) reduced angiogenesis. The messenger RNA (mRNA) level of EfnB2 increased significantly in the hyperoxic phase (P7-P12), while EphB4, VEGF, VEGFR1 and VEGFR2 showed a significant - up to fivefold - increased expression at P14, the start of morphologically visible vasoproliferation caused by relative hypoxia. CONCLUSION: The ephrin/Eph system is involved in angioproliferative retinopathy. Stimulation of EphB4 and EfnB2 signalling using EfnB2-Fc and EphB4-Fc, respectively, enhanced hypoxia-induced angiogenesis. In contrast, sEphB4 inhibited hypoxia-induced angiogenesis. Therefore, angiogenesis is enhanced by signalling through both EphB4 (forward) and EfnB2 (reverse). The distinction in the expression kinetics of EphB4 and EfnB2 indicates that they govern two different signalling pathways and are regulated in diverse ways. sEphB4 might be a useful drug for antiangiogenic therapy.

Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study.

OBJECTIVE: The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center. RESEARCH DESIGN AND METHODS: This was a 12-month, multicenter, sham-controlled, double-masked study with eyes (age>18 years, type 1 or 2 diabetes, central retinal thickness [CRT]≥300 µm, and best corrected visual acuity [BCVA] of 73-39 ETDRS letters [Early Treatment Diabetic Retinopathy Study]) randomly assigned to intravitreal ranibizumab (0.3 or 0.5 mg; n=51 each) or sham (n=49). The treatment schedule comprised three monthly injections, after which treatment could be stopped/reinitiated with an opportunity for rescue laser photocoagulation (protocol-defined criteria). After month 1, dose-doubling was permitted (protocol-defined criteria, injection volume increased from 0.05 to 0.1 ml and remained at 0.1 ml thereafter). Efficacy (BCVA and CRT) and safety were compared between pooled ranibizumab and sham arms using the full analysis set (n=151, patients receiving≥1 injection). RESULTS: At month 12, mean±SD BCVA improved from baseline by 10.3±9.1 letters with ranibizumab and declined by 1.4±14.2 letters with sham (P<0.0001). Mean CRT reduction was 194.2±135.1 µm with ranibizumab and 48.4±153.4 µm with sham (P<0.0001). Gain of ≥10 letters BCVA from baseline occurred in 60.8% of ranibizumab and 18.4% of sham eyes (P<0.0001). Safety data were consistent with previous studies of intravitreal ranibizumab. CONCLUSIONS: Ranibizumab is effective in improving BCVA and is well tolerated in DME. Future clinical trials are required to confirm its long-term efficacy and safety.

Vitreal levels of erythropoietin are increased in patients with retinal vein occlusion and correlate with vitreal VEGF and the extent of macular edema.

PURPOSE: This study compares vitreal levels of erythropoietin (EPO) in patients with retinal vein occlusion (RVO) with control subjects. In addition, it investigates different RVO disease parameters (time of vein occlusion, patient age, vitreal vascular endothelial growth factor (VEGF) levels, and extent of central macular edema) for possible correlations with vitreal EPO levels. METHODS: Serum and vitreal EPO were measured from 6 patients with branch retinal vein occlusion, 6 patients with central retinal vein occlusion, and 12 control subjects (10 macular puckers and 2 macular holes). RESULTS: Serum EPO levels (9.8 ± 4.9 mU/mL) did not differ between the RVO and control groups and were significantly lower than vitreal EPO levels in all groups. Vitreal EPO was elevated both in branch RVO (91 ± 59 mU/mL) and central RVO (182 ± 70 mU/mL) compared with controls (35 ± 24 mU/mL). Increased vitreal EPO correlated with higher vitreal VEGF (r = 0.64, P = 0.0008) and more pronounced central macular edema (r = 0.66, P = 0.001). CONCLUSION: The results from this study indicate that EPO is locally expressed in the retina and that it is upregulated together with VEGF in RVO eyes. Because of its role both in neuroprotection and angiogenesis, ocular EPO might represent an interesting target to investigate in patients with RVO, especially in light of the current anti-VEGF treatments.

Intravitreal bevacizumab (Avastin) vs. ranibizumab (Lucentis) for the treatment of age-related macular degeneration: a systematic review.

PURPOSE OF REVIEW: We conducted a systematic review to evaluate whether the existing evidence justifies the intravitreal use of bevacizumab in comparison to ranibizumab in age-related macular degeneration. RECENT FINDINGS: Compared with photodynamic therapy, bevacizumab shows a relative improvement in visual acuity that is of similar size as in the comparison of ranibizumab with photodynamic therapy (relative improvement from 30 to 35%). However, this finding is based on one randomized controlled trial including less than 50 patients treated with bevacizumab. Also, nothing is known about long-term (>12 months) improvements in visual acuity and optimal treatment intervals for bevacizumab.Regarding safety, the published literature indicates that ocular and systemic adverse effects are less frequent under bevacizumab than ranibizumab treatment. But the validity of this finding is strongly limited by inadequate reporting, an unsystematic evaluation of adverse effects and short follow-up times in studies evaluating bevacizumab. SUMMARY: Given the lack of controlled data, the widespread off-label use of bevacizumab is not justified in clinical practice. On the other hand, a major challenge in the management of patients who require repeated antivascular endothelial growth factor injections is the high cost of ranibizumab. This dilemma underlines the need for head-to-head studies comparing both vascular endothelial growth factor antibodies, or, at least, well conducted randomized controlled trials evaluating intravitreal bevacizumab.

Bevacizumab in central retinal vein occlusion: a retrospective analysis after 2 years of treatment.

PURPOSE: Bevacizumab (Avastin) was first used clinically in 2005. Reports on the treatment of more than 600 patients with central retinal vein occlusion (CRVO) have been published to date. However, there are limited data on the long-term effects of bevacizumab in patients with CRVO. METHODS: We retrospectively re-evaluated 10 patients with CRVO who were initially part of one of the first published case series on the short-term effects of bevacizumab. The patients were invited for a follow-up visit 2 years after their initial bevacizumab injection. Study endpoints were changes in visual acuity (VA) and central macular edema (CME) compared to 1) baseline values and 2) short-term values after the initial injection. RESULTS: Short-term VA gain had been 2.9 lines 3 weeks after the first bevacizumab injection. Two years later, mean VA gain vs baseline was 1.6 lines. Low baseline VA and good response to the first injection correlated positively with higher long-term VA gains (Pearson correlation of r = 0.50 and r = 0.66). There was no correlation for injection number, occlusion time, or CME changes with long-term VA gain. CONCLUSIONS: The initial short-term VA gain after bevacizumab treatment was not always maintained over a 2-year period despite repeated injections. Patients with low baseline VA and good response to the first injection seemed to benefit most from repeated bevacizumab injections.

Combinatory inhibition of VEGF and FGF2 is superior to solitary VEGF inhibition in an in vitro model of RPE-induced angiogenesis.

BACKGROUND: Choroidal neovascularisation (CNV) as a feature of exudative age-related macular degeneration (AMD) is partially regulated by retinal pigment epithelium (RPE). In this study, the effect of combinatory anti-angiogenic treatment was evaluated using a novel in vitro assay of RPE-induced angiogenesis. METHODS: RPE isolated from surgically excised CNV-membranes (CNV-RPE) was used to stimulate sprouting of endothelial cell (EC) spheroids in a 3D collagen matrix. The anti-angiogenic effect of solitary anti-VEGF antibodies (bevacizumab) was compared to a combinatory treatment with anti-VEGF and anti-FGF2 antibodies. RESULTS: Anti-VEGF treatment inactivated all RPE-derived VEGF but was unable to fully inhibit EC sprouting induced by CNV-RPE. Combined anti-VEGF/anti-FGF treatment inactivated both growth factors and reduced EC sprouting significantly. CONCLUSIONS: RPE from CNV patients expresses angiogenic growth factors that act in part independently of VEGF. Targeted combinatory therapy can be superior to solitary anti-VEGF therapy. One possible candidate for combinatory therapy is FGF2.

Histopathological findings after retinal endovascular lysis in central retinal vein occlusion.

This case study explores the histopathological findings 9 months after retinal endovascular lysis (REVL) in a 62-year-old woman having a 7-week-old, highly ischaemic central retinal vein occlusion (CRVO) with hand movement vision. Angiographic examination 3 days postoperatively did not show improved arteriovenous passage time. In addition, the patient's postoperative vision did not change, and despite intensive photocoagulation and cryotherapy in the early postoperative period, the globe had to be removed 9 months later because of painful phthisis. Histological findings at the site of puncture were epiretinal membrane, interrupted internal limiting membrane and thickened venous wall. This is the first case to show the histological changes after surgical REVL in a human eye. In this case, REVL did not prevent neovascular glaucoma despite successful recombinant tissue plasminogen activator (rt-PA) injection in a venous branch close to the papilla. It was concluded that rt-PA injection after 7 weeks of CRVO is too late.

Syndromic choroideremia: sublocalization of phenotypes associated with Martin-Probst deafness mental retardation syndrome.

PURPOSE: To identify the mutation leading to syndromic choroideremia (CHM) in two families and to define fundus autofluorescence (FAF) in CHM carriers. METHODS: The ophthalmic and clinical phenotype was investigated including FAF, neuropediatric, otorhinolaryngologic, cardiologic, and nephrologic examinations of three male patients (age, 11-46 years) and three female carriers (age, 11-46 years) from two families. Genomic DNA amplification (PCR) of the REP1 gene as well as adjacent loci was used to determine the molecular basis of the phenotype. RESULTS: Analysis of genomic DNA revealed large deletions that asymmetrically flank REP1 in both families, ranging from a minimum size of 6.3 and 8.5 mega base pairs (Mbp) to a maximum size of 9.7 and 14.1 Mbp, respectively. In addition to CHM, patients from these families exhibited mild syndromic features, including mental and motor retardation and low-frequency hearing loss. FAF showed a distinctive pattern characterized by small areas of reduced and increased autofluorescence in all female carriers. CONCLUSIONS: Both CHM families are the first to be described with large deletions that manifest with a mild syndromic phenotype. The location of the deletions indicates that they may allow sublocalization of the syndromic features to the most proximal region of X-linked distal spinal muscular atrophy (DSMAX) and Martin-Probst deafness mental retardation syndrome (MPDMRS). The FAF pattern is specific to CHM carriers and thus will help to identify and differentiate between carriers of other X-linked recessive carrier states such as in X-linked retinitis pigmentosa.

Retinal vascular occlusions: an interdisciplinary challenge.

INTRODUCTION: Retinal venous and arterial occlusions are common causes of visual loss. Depending on the location and extent, symptoms may vary from very discrete impairments to complete loss of sight. METHODS: Selective literature review including the authors' own research data with a particular focus on interdisciplinary aspects. RESULTS: Retinal vascular occlusions are not a uniform entity. Rather, they reflect the whole breadth of vascular disease. In arterial occlusion, embolic phenomena and Horton's arteritis should be excluded, in addition to local ophthalmological investigations. In retinal venous occlusion, optimal treatment of arterial hypertension is universally useful, while investigations for thrombophilia are useful in patients under 50 years of age. The results of intravitreal injection of corticosteroids and vascular endothelial growth factor inhibitors appear encouraging in treatment of macular edema secondary to retinal vein occlusion. DISCUSSION: While local diagnostic and therapeutic measures are performed by ophthalmologists, there is an important role for interdisciplinary cooperation in the investigation and systemic treatment of these events.

Annular fundus autofluorescence abnormality in a case of macular dystrophy.

PURPOSE: To present a case of macular dystrophy with early changes in fundus autofluorescence. METHODS: A 20-year-old woman with a recent loss of visual acuity and onset of photophobia was examined. Color vision and visual field testing, fluorescein angiography, full-field and multifocal electroretinograms as well as fundus autofluorescence were performed. RESULTS: Best-corrected visual acuity was 20/100 (right eye) and 20/60 (left eye). There was a red-green color vision defect and a relative central scotoma in both eyes. Ophthalmoscopy and fluorescein angiography were essentially normal, the presence of a dark choroid was debatable. Full-field ERG responses were normal, but the multifocal ERG showed severely reduced responses in the macular region. Both eyes showed a slight circular parafoveolar increase of fundus autofluorescence. CONCLUSION: Besides multifocal ERG, fundus autofluorescence aids to objectively assess the manifestation of macular dystrophies but does not discern between different types in early stages.