[Less Frequent Vascular Disorders of the Retina - Part 1]. / Seltene vaskuläre Erkrankungen der Netzhaut ­ Teil 1.

This review provides an overview of retinal vascular disorders that are less frequent in Germany and Europe compared to diabetic retinopathy and retinal venous or arterial occlusive disorders. The knowledge of these disorders is important for the differential diagnosis of retinal vascular disorders as well as potentially associated systemic disorders. In the current part one epidemiology, pathophysiology, clinical presentation, and therapy are discussed for hypertensive retinochoroidopathy, ocular ischemic syndrome, retinal alterations in sickle cell disease, Eales disease, radiation retinopathy, peripheral exudative hemorrhagic chorioretinopathy, and retinal disorders associated with pregnancy.

Incidence of Retinal Detachment after Macular Surgery. / Ablatiohäufigkeit nach elektiver Makulachirurgie.

Macular surgery has become an increasingly atraumatic procedure for the eye with the surgical methods that have been further developed in recent years. The most common complications include cystoid macular oedema and retinal detachment, more rarely endophthalmitis. The aim of this retrospective study is to record the number of retinal detachments following elective macular surgery. In this study we included all patients who underwent pars plana vitrectomy (ppV, 20 or 25 gauge) in the years 2009 - 2016. We then identified the patients who were hospitalised again because of retinal detachment. For the affected patients, the rate of retinal detachment, functional outcomes and possible risk factors were recorded. A total of 904 eyes were identified, of which 667 had surgery for epiretinal membrane, 188 for macular hole, and 49 for vitreomacular traction with a 20 or 25 gauge ppV. Of these 904, retinal detachment occurred in 17 (1.88%) cases. The mean time between first ppV and second ppV with retinal detachment was 248 days (3 - 1837 days). Two of the 17 patients had at least one retinal break before or during surgery. The retinal break was located inferior in six cases, superior in four; in four cases PVR retinal detachment and in three cases the foramina were distributed. Mean visual acuity was 0.27 (decimal) before macular surgery and 0.28 at the time of last presentation. Modern vitrectomy techniques reduce the complications in elective macular surgery, but do not replace the surgeon's experience.

Treatment of radiation-induced maculopathy with fluocinolone acetonide.

PURPOSE: Chronic macular oedema is a well-known presentation of radiation-induced maculopathy (RM) following external beam photon therapy, plaque radiotherapy and proton beam radiotherapy for choroidal tumours. Current therapies vary in respect of efficacy and clinical benefit. The potential of fluocinolone acetonide (FAc) slow-release implants is unknown. We hypothesised that local continuous delivery of low-dose corticosteroids might improve symptoms of RM. METHODS: Five-two male and three female-patients from 37 to 68 years presented with RM following 106Ru-plaque brachytherapy or stereotactic radiation therapy (STx) with photons using a hypofractionated schedule of 5 × 10 Gy. All were treated with triamcinolone injections in first line and proofed to be refractory to steroids. In addition, two patients had received Ozurdex® implants as a second-line treatment, though without any clinical benefit. FAc slow-release implants were injected, and patients were followed up to monitor clinical improvement. RESULTS: All patients responded to therapy by means of a decrease in macular oedema. In four of five (80%) patients, visual acuity improved, and one patient showed stable visual acuity. No toxic effects or complications were observed. CONCLUSION: Slow-release implants of FAc are a promising therapeutic potent steroid treatment option to benefit anatomical structures of the fovea and visual function. Slow-release implants with FAc reduce the frequency of intravitreal injections and the therapeutic burden.

Stereotactic radiotherapy for choroidal melanomas by means of HybridArc™ : Physics and technique of linac-based photon beam therapy.

PURPOSE: Stereotactic radiotherapy (SRT) is suitable to treat ocular tumours. The optimal beam geometry for SRT, however, has not been defined. Here we evaluate a combination technique with dynamic conformal arcs (DCAs) and intensity-modulated static fields (IMRT), known as HybridArc™ (HA). METHODS: For the first consecutive 25 cases with choroidal melanomas with volumes of 0.02 to 1.18 cm3 treated with 50 Gy in five fractions, the results with respect to dose conformity, homogeneity, and dose distributions were summarised. To describe the dose distribution at the planning target volume (PTV) boundary, we defined a spatially averaged dose gradient (SADG) and compared it with Paddick's gradient index (GI). We made dosimetric comparisons between HA and other irradiation techniques. RESULTS: The PTVs ranged from 0.42 to 3.37 cm3. The conformity index (CI) was 1.25 ± 0.15, and the homogeneity index (HI) 0.08 ± 0.02. The SADG was (-3.5 ± 0.5) Gy/mm or (-7.0 ± 1.0) %/mm between the isodose levels 95 and 20%; local minima reached -11.5 Gy/mm or -22.9%/mm. The coefficient of determination for a nonlinear regression of GI on SADG was 0.072. After a median follow-up time of 19.6 months, local tumour control was 100% without any case of post-therapeutic enucleation. Two patients (8%) developed liver metastases. CONCLUSION: SRT of ocular tumours by HA is highly appropriate, and HA is superior to intensity-modulated arc therapy (IMAT) concerning dose reduction in organs at risk (OARs). The novel gradient measure SADG is more informative than Paddick's GI.

Impact of tumour volume and treatment delay on the outcome after linear accelerator-based fractionated stereotactic radiosurgery of uveal melanoma.

BACKGROUND/AIMS: Primary radiation therapy is used to treat malignant uveal melanoma (UM). We report our single-centre experience with fractionated radiosurgery (fSRS) with a linear accelerator (LINAC) after specific adaptation for small target volumes with HybridArc. METHODS: From October 2014 to January 2020, 101 patients referred to Dessau City Hospital with unilateral UM underwent fSRS with 50 Gy given in five fractions on five consecutive days. Primary endpoints were local tumour control, globe preservation, metastasis and death. Potential prognostic features were analysed. Kaplan-Meier analysis, Cox proportional hazards model and linear models were used for calculations. RESULTS: The median baseline tumour diameter was 10.0 mm (range, 3.0-20.0 mm), median tumour thickness 5.0 mm (range, 0.9-15.5 mm) and median gross tumour volume (GTV) 0.4 cm³ (range, 0.2-2.6 cm³). After a median follow-up of 32.0 months (range, 2.5-76.0 months), 7 patients (6.9%) underwent enucleation: 4 (4.0%) due to local recurrence and 3 (3.0%) due to radiation toxicities, and 6 patients (5.9%) revealed tumour persistence with a GTV exceeding 1.0 cm³. Of 20 patients (19.8%) who died, 8 (7.9%) were tumour-related deaths. Twelve patients (11.9%) suffered from distant metastasis. GTV showed an impact on all endpoints, and treatment delay was associated with reduced odds of eye preservation. CONCLUSION: LINAC-based fSRS with static conformal beams combined with dynamic conformal arcs and discrete intensity-modulated radiotherapy results in a high tumour control rate. The tumour volume is the most robust physical prognostic marker for local control and disease progression. Avoiding treatment delay improves outcomes.

Endogenous filamentous fungal endophthalmitis--single-centre survey in patients with acute leukaemia or postallogeneic stem cell transplantation and review of the literature.

Endogenous endophthalmitis caused by filamentous fungi has been infrequently described and its prognosis in immunocompromised patients is largely unknown. Patients were identified through a single-centre database containing patients with endophthalmitis. Cases published since 2002 were reviewed. Clinical and treatment features as well as outcomes were analysed. Six patients were identified from the database. Underlying conditions were haematological malignancies (HM) and/or allogeneic haematopoietic stem cell transplantation (HSCT). Three patients underwent vitrectomy. None of the patients survived and the median time from first evidence of endophthalmitis until death was 33 days. The median time from first evidence of an invasive fungal infection to endophthalmitis was only 5 days. Fifty-six patients were identified from the literature. The majority of these patients underwent vitrectomy (27) or enucleation (10) and received intraocular antifungal therapy (28). Only 13 (23%) of 56 patients experienced an improved vision. The survival rate was 52% in all 56 patients but was significantly less in patients with HM or post-HSCT when compared with all others (26% vs. 70%, respectively; P = 0.003). Endogenous endophthalmitis caused by filamentous fungi is frequently associated with a permanent decrease or loss of vision. This type of fungal infection carries a particular poor prognosis in patients with profound immunosuppression, requiring improved treatment strategies.

Ocular involvement in Adamantiades-Behçet's disease in Berlin, Germany.

BACKGROUND: Epidemiological studies demonstrate a prevalence of Adamantiades-Behçet's disease (ABD) in the range of 0.12-420 per 100,000 inhabitants, with the highest rates in Istanbul, Turkey, and the lowest rates in the USA. Ophthalmological data on the prevalence of ocular involvement are limited for ABD in Germany, because most epidemiological studies are based on rheumatological or dermatological data. Berlin is the city with the highest number of non-native German inhabitants, and its multi-ethnic character renders it uniquely appropriate for epidemiological studies on ABD. METHODS: We retrospectively analyzed all ABD patients seen in our department since 1982. All patients fulfilled the criteria of the International Study Group for Behçet's Disease. We found 140 patients (63 female, 77 male), with a mean follow-up of 6.4 years (0.5-22 years). RESULTS: The mean age was 23 at the first manifestation and 32 when the full-blown disease was noted. The mean age at onset of ocular involvement was 30. Most of the patients were of Turkish (n = 73) or German (n = 34) origin. Fifty-six percent developed ocular involvement, which was the first manifestation in 8.6% and the second manifestation in 19.3% of cases. CONCLUSIONS: More than half the patients developed ocular involvement. The calculated prevalence of ocular involvement in ABD is 1.77/100,000 inhabitants for the municipality of Berlin.

Incidence and outcome of endophthalmitis over a 13-year period.

OBJECTIVE: The aim of the study was to assess the functional results and long-term visual prognosis in patients treated for acute endophthalmitis (AE). DESIGN: Observational clinical series. PARTICIPANTS: Evaluation of 120 eyes of 114 patients with AE treated between 1991 and 2004. METHODS: This retrospective institutional analysis included 120 eyes of 114 patients (52 male, 68 female) with AE and a minimum follow-up of half a year. The patients had a mean follow-up of 23 months (6-135 months) and a mean age of 61 years (8 months-94 years) at the time of treatment. Treatment included intraocular injection of antibiotics alone (n = 18, 15%) and vitrectomy combined with intraocular and topical postoperative antibiotics (n = 85, 70%). RESULTS: The most frequent complications were vitreous or retinal hemorrhages (n = 17, 14%), retinal detachment (n = 17, 14%), choroidal detachment (n = 3, 3%), secondary glaucoma (n = 7, 6%), and recurrent endophthalmitis (n = 3, 3%). Four eyes had to be enucleated because of recurrent and uncontrollable infection. Positive microbiological results were achieved in 67 of 88 specimens (76%). The most common isolate was Staphylococcus. At the end of follow-up, visual acuity was reduced (more than 2 lines) in 18 eyes (15%), stable in 22 (18%), and improved (more than 2 lines) in 72 eyes (60%). CONCLUSIONS: AE is a rare but severe disease with a potentially deleterious outcome in affected eyes. In our series, 78% of all eyes had stable or improved postoperative visual acuity following various treatment regimens, depending on the severity of each case.

Implantation of scleral fixated sutured posterior chamber lenses: a retrospective analysis of 119 cases.

BACKGROUND: The implantation of scleral fixated sutured posterior chamber lenses enables lens implantation in the absence of adequate lens capsule support. Anterior chamber lenses and their side effects can also be avoided, particularly in cases of unilateral aphakia and contact lens incompatibility. METHODS: This study is a retrospective analysis of 119 scleral fixated sutured posterior chamber lenses implanted in 115 patients. Seventy-nine cases of damaged zonula or damaged lens capsule and 17 cases of corneal decompensation secondary to anterior chamber lenses were the main indications for the suture fixation. The mean follow-up was 23 months (6-83 months). RESULTS: In 50% of all cases, improved visual acuity was achieved. Twenty-four percent of patients showed unchanged visual acuity, while 26% had poorer vision postoperatively, mainly because of corneal decompensation following anterior chamber lens explantation. The main postoperative complication was transient rise of intraocular pressure, occurring in 44% of the cases. CONCLUSIONS: In most cases improved or comparable postoperative visual acuity was achieved. The main complication observed was postoperative glaucoma, especially in patients with pre-existing glaucoma.

Optimizing radiosurgery with photons for ocular melanoma.

BACKGROUND AND PURPOSE: Photon radiotherapy has been established for the treatment of ocular melanoma (OM). Here we investigate the planning qualities of two different planning approaches, a combination of dynamic conformal arcs (DCA) complemented with multiple non-coplanar static intensity-modulated (IMRT) fields (DCA-IMRT), and volumetric modulated arc therapy (VMAT) in combination with automated planning (AP). MATERIALS AND METHODS: Thirteen consecutive patients treated for ocular melanoma with curative intent on a Linac-based radiosurgery system were analyzed. Fractionated stereotactic radiosurgery (fSRS) was applied using 50 Gy in 5 fractions using the combination of DCA-IMRT. Plans were reviewed and the thirteen cases were compared to plans obtained with optimized automated VMAT based on a set of 28 distinct patients treated with DCA-IMRT who were selected to generate the AP model for the prediction of dose volume constraints. RESULTS: Overall, plan quality of DCA-IMRT was superior to AP with VMAT. PTV coverage did not exceed 107% in any case treated with DCA-IMRT, compared to seven patients with VMAT. The median PTV covered by >95% was 98.3% (91.9%-99.7%) with DCA-IMRT, compared to 95.1% (91.5%-97.9%) (p < 0.01) with VMAT. The median mean dose delivered to the treated eye was 22.4 Gy (12.3 Gy-33.3 Gy) with DCA-IMRT compared to 27.2 Gy (15.5 Gy-33.7 Gy) (p < 0.01). Dose to the ipsilateral lacrimal gland and the ipsilateral optic nerve were comparable for DCA-IMRT and VMAT, however, the dose to the lens was lower with DCA-IMRT compared to VMAT. CONCLUSIONS: The combination of multiple arcs complemented with multiple IMRT fields sets the gold standard for fSRS of ocular melanoma for photon therapy.

Retinal angiomatosis in von Hippel-Lindau disease: a longitudinal ophthalmologic study.

OBJECTIVE: To characterize the clinical course of retinal angiomatosis (RA) in von Hippel-Lindau (VHL) disease. DESIGN: Retrospective observational case series from a tertiary referral center. PARTICIPANTS: Fifty-seven consecutive VHL disease patients with RA with a mean follow-up of 7.3 years. METHODS: A retrospective chart review was performed to characterize the clinical course and functional outcome of RA to substantiate ophthalmic screening recommendations for VHL disease patients. MAIN OUTCOME MEASURES: Age and visual acuity (VA) at diagnosis, angioma number, size, fundus position and growth behavior, functional outcome, and risk factors for adverse visual outcome (VA < or =20/1000) were evaluated. RESULTS: The onset of RA was observed to occur between the ages of 5.5 and 62.5 years. Ocular disease was unilateral in 58% of patients at diagnosis; prevalence of bilateral RA as calculated by Kaplan-Meier analysis was 100% at age 56.4 years. Twenty-seven eyes showed an adverse visual outcome, occurring at a mean age of 23.2 years. Risk factors included large angiomas at presentation, first manifestation at a younger age, and symptomatic RA. In most eyes, development of new angiomas was slow and only small angiomas were detected on annual follow-up. Eyes harboring multiple angiomas or RA complicated by retinal detachment were at risk of developing large angiomas after short follow-up intervals. Formation of new angiomas was largely independent of patient age. CONCLUSIONS: Retinal angiomatosis in VHL disease bears a high risk of severe vision loss at a young age. In uncomplicated RA, annual ocular screening for presymptomatic angiomas is sufficient. Because RA can occur at any age, lifelong ocular screening is recommended in VHL disease gene carriers starting at preschool age.

Neoadjuvant proton beam irradiation followed by transscleral resection of uveal melanoma in 106 cases.

AIMS: To describe results after neoadjuvant proton beam irradiation followed by transscleral resection of large uveal melanoma. METHODS: Retrospective interventional case series, including 106 consecutive patients. Local tumour control, enucleation and metastasis development were assessed with survival curves. Predictors of local recurrence and metastasis were investigated with log-rank testing. RESULTS: Mean follow-up was 3.2 years. Local recurrence occurred in five cases with an estimated risk of 4.2% and 10.4% at 3 and 5 years after treatment, respectively. Enucleation was performed in 10 cases with an estimated risk of 9.2% and 18.4% at 3 and 5 years, respectively. Significant risk factors for local recurrence were not evident. Metastasis was estimated to occur in 28.4% at 3 years and 40.3% at 5 years, correlating with patient's age only (p=0.01). Seventy four patients (69.8%) underwent vitreoretinal surgery for complications after tumour resection. Median visual acuity (VA) was 20/50 at diagnosis and 20/400 in the third year after treatment. VA preservation of 20/200 or better was achieved in 33 patients (31.1%). CONCLUSION: Neoadjuvant proton beam irradiation may help to prevent local recurrence after transscleral resection. Additional vitreoretinal surgery was frequently needed in the presented series. The majority of patients avoided enucleation and functional blindness.

Indocyanine green angiography and fluorescein angiography of malignant choroidal melanomas following proton beam irradiation.

BACKGROUND: The vascularisation features of intraocular tumours may be characterised by indocyanine green angiography (ICG-A) and fluorescein angiography (FA). Proton beam irradiation is an established method of treating malignant melanoma of the choroid. The aim of this study was to describe the vascularisation features of small choroidal melanomas and to examine the influence of proton beam irradiation on these tumours. METHODS: We examined 39 choroidal melanomas by ICG-A and FA from 1998 to 2001 in a prospective study. The tumours had a mean prominence of 3.65 mm (1.2-7.5 mm) and a common feature of all was their parapapillary or paramacular localisation. Angiography was always performed immediately before proton beam radiotherapy and at intervals of 3 months, half a year and 1 year thereafter. Two hundred and forty angiographies were analysed in total. RESULTS: Intra-tumoral vessels could be visualised in 89% of all tumours by ICG angiography but in only 33% by FA. Neither ICG-A nor FA detected changes 3 months after irradiation; however, ICG-A disclosed strong leakage from vessels in the tumour area after 6 months. These changes increased markedly after 12 months and were also visible by FA. A disadvantage of FA, however, was the faster escape of dye from the vessels, which caused rapid leakage in the tumour area and meant that details could no longer be demonstrated. CONCLUSIONS: ICG-A and FA detect marked vascular changes within the tumours examined.

An epidemiological study of neovascular age-related macular degeneration in Germany.

OBJECTIVE: Neovascular or wet age-related macular degeneration (AMD) is one of the leading causes of blindness in industrialized countries; however, there is a lack of recent epidemiological data from Germany. The aim of this study was to collect epidemiological data from patients in Germany with suspected neovascular AMD and evaluate the diagnostic procedures performed and treatments used at clinics. METHODS: This was a Germany-based, multicentre, retrospective review of data from patients with suspected neovascular AMD visiting ophthalmology clinics over an 18 month period in 2008-10. Clinical characteristics, functional symptoms and examination results were recorded. In addition, ophthalmologists completed a questionnaire on neovascular AMD diagnosis and treatment. RESULTS: Ten sites collected data from 2498 patients (64.0% female) with a mean decimal visual acuity of 0.4 ± 0.3 at the time of diagnosis of neovascular AMD. The mean age at the time of diagnosis was 76.9 ± 8.9 years for patients with the right eye affected and 77.0 ± 8.3 years for patients with the left eye affected. The most frequent pathological findings detected by routine ophthalmic examination were old lesions (31.2%), intra/subretinal fluid (18.1%), new lesions (13.0%), and intra/subretinal haemorrhage (11.4%). A confirmed diagnosis of neovascular AMD was most frequently based on fundoscopy (67.3%), fluorescein angiography (39.6%), and biomicroscopy (35.7%) tests but rarely on optical coherence tomography (8.9%). The most frequently documented comorbidity with neovascular AMD was hypertension and other cardiovascular diseases (57.5%). Seven ophthalmologists completed the questionnaire with the majority of ophthalmologists agreeing that regular ophthalmic examination can prevent the development of late-stage neovascular AMD. CONCLUSION: Neovascular AMD is a frequent diagnosis in German ophthalmology clinics. As visual acuity is already poor in most patients with suspected neovascular AMD, regular preventive ophthalmologic examinations should be considered in high risk patients. STUDY LIMITATIONS: Limitations of the study include the lack of a comparator cohort, which limited the amount of analyses that could be performed. Additionally, a study eye was not defined and information was collected separately for each affected eye and therefore analysed separately. Furthermore, a small number of ophthalmologists completed the questionnaire, limiting the objectivity.

Results and complications after implantation of a black iris-lens diaphragm in patients with traumatically induced aphakia and aniridia.

PURPOSE: The black iris-lens diaphragm (ILD) can be used in the treatment of traumatic aniridia and aphakia. The aim of our study was to show postoperative functional and anatomic results and complications in a small case series. METHODS: We retrospectively analyzed the files of 16 patients managed with a black ILD or a sole iris diaphragm in the period 1994-2007. Four of them were female and 12 were male. The mean age of the group was 50±17 years. At the time of the implantation, all of the eyes had already undergone primary surgical repair. RESULTS: The preoperative best-corrected visual acuity in half of the patients was =0.1 and remained stable after the first postoperative year. During the follow-up years, one eye developed a subluxation of the implant and one eye an anterior chamber hemorrhage. At the same time, out of 8 eyes carrying a silicone tamponade in the vitreous cavity, silicone oil entered the anterior chamber in 3 cases. In one case, enucleation was undertaken due to phthisis. CONCLUSIONS: In the case of severely traumatized eyes with aniridia and aphakia, the implantation of a black ILD can have a positive effect on functional and anatomic stabilization.

Ten-year results of transscleral resection of large uveal melanomas: local tumour control and metastatic rate.

AIMS: To describe the long-term tumour control and metastatic rate after transscleral resection (TSR) of large uveal melanomas in a single-centre study. METHODS: The sample included 210 patients with large uveal melanomas. Univariate analysis of local tumour control and metastatic risk by Kaplan-Meier survival curves and log-rank testing. Cox proportional HR analysis with forward and backward selection was used to identify independent prognostic factors in patients submitted to TSR of a large uveal melanoma. RESULTS: A residual tumour was diagnosed in 6% of the patients. The 5- and 10-year local tumour recurrence rates were 24% and 32%, respectively. Older age, a large basal tumour diameter, the lack of adjuvant ruthenium brachytherapy and retinal detachment led to a 2.6, 2.4, 4.4 and 7.8 times higher risk of melanoma recurrence, respectively. The 5- and 10-year metastatic rates were 28% and 44%, respectively, and were statistical significantly affected by extraocular spread, tumour thickness and local tumour recurrence. CONCLUSIONS: TSR is an alternative to enucleation for the treatment of large uveal melanomas. Results should improve with better patient selection and more effective methods of adjuvant radiotherapy.

Ocular syphilis--indicator of previously unknown HIV-infection.

OBJECTIVES: To detect the prevalence of HIV-co-infection in patients with ocular syphilis and to compare ocular syphilis in HIV-positive and -negative patients. METHODS: 24 consecutive patients treated for ocular syphilis at our hospital between 1998 and 2006 were evaluated retrospectively. Patients' characteristics, laboratory results (including syphilis serology, HIV status, CSF examination), major ophthalmologic finding, treatment and course were assessed. Data of HIV-positive and -negative patients were compared. RESULTS: Of the 24 patients with ocular syphilis, 11 were co-infected with HIV. Notably, the HIV-infection had previously been unknown in 7 of the 11 HIV-positive patients. 6 of these were in an early disease stage (CDC category A). Clinical and laboratory findings did not differ between HIV-positive and -negative patients except for the C-reactive protein (CRP), which was significantly higher in HIV-infected patients. CONCLUSIONS: Ocular syphilis led to new diagnosis of HIV-infection in an unexpectedly high number of patients, which emphasises that patients with ocular syphilis must be screened for HIV-co-infection. According to our study the expected benefit is high because most of the patients newly diagnosed with HIV had high CD4(+) cell counts. These patients can be monitored and treated before the development of AIDS.