Atypical macular hole formation after Anti-VEGF therapy for neovascular age-related macular degeneration: Coincidence or consequence?

INTRODUCTION AND OBJECTIVES: Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries, particularly in older adults. Anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection is the current standard treatment for neovascular form of AMD. Studies reporting macular hole (MH) formation following anti-VEGF treatment are limited, and the exact pathogenesis is still under discussion. With the present study, we aim to analyse the clinical features of eyes developing MH after anti-VEGF therapy for neovascular AMD. MATERIALS AND METHODS: Patients were treated with intravitreal anti-VEGF agents for at least one year and stable for at least six months. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were evaluated. RESULTS: Nineteen eyes of 18 patients were included in this study. Patients had an average age of 77.7 years at first visit and eight were female. The average number of injections before the MH formation was four. MH developed after a mean follow-up of 5.1 months after the last injection. Sixteen eyes had (84.2%) had choroidal neovascular membrane without any abnormal vitreomacular traction. Eleven eyes (57.8%) had retinal pigment epithelium detachment (PED), two (10.5%) had an epiretinal membrane (ERM), and one (5.2%) had retinal pigment epithelium (RPE) tear. The mean first and last BCVA was 1.07±0.48 LogMAR (0.3-1.8) and 1.16±0.38 logMAR (0.4-1.8), respectively. CONCLUSIONS: A macular hole can be observed in AMD patients receiving anti-VEGF therapy. Increased fibrovascular scar tissue due to subretinal fluid resolution, neovascular membrane contraction, and the presence of PED, RPE tear, and ERM may contribute to MH formation.

Formación atípica de agujero macular después de terapia Anti-VEGF para la degeneración macular asociada a la edad: ¿coincidencia o consecuencia? / Atypical macular hole formation after Anti-VEGF therapy for neovascular age-related macular degeneration: Coincidence or consequence?

Introducción y objetivos La degeneración macular asociada con la edad (DMAE) es la causa primaria de ceguera en los países desarrollados, especialmente en adultos mayores. Actualmente, la inyección intravítrea del factor de crecimiento endotelial vascular (VEGF) es el tratamiento estándar para la forma neovascular de la DMAE. Existen pocos estudios que informen sobre la creación de un agujero macular (AM) después de un tratamiento anti-VEGF, y la patogénesis exacta de AM permanece en debate. El presente estudio tiene por objetivo analizar las características clínicas de los ojos que desarrollan AM después de recibir terapia anti-VEGF para la DMAE neovascular. Materiales y métodos Los pacientes fueron tratados con agentes anti-VEGF intravítreos durante al menos un año, permaneciendo estables por, al menos, seis meses. Se evaluaron la mejor agudeza visual corregida (MAVC) y los hallazgos de tomografía de coherencia óptica. Resultado Se incluyeron en el estudio 19 ojos de 18 pacientes. La edad media de los mismos fue de 77,7 años en la primera visita. Ocho eran de sexo femenino. El número medio de inyecciones antes de la formación de un AM fue de cuatro. El AM se desarrolló después de un seguimiento medio de 5,1 meses desde la última inyección. Dieciséis ojos (84,2%) exhibieron membrana coroidal neovascular sin tracción vitreomacular anormal. Once ojos (57,8%) mostraron desprendimiento del epitelio pigmentario (DEP) de la retina, dos (10,5%) tuvieron membrana epirretinal (MER) y uno (5,2%) presentó desgarro del epitelio pigmentario de la retina (PER). La media de la MAVC fue de 1,07 ± 0,48 LogMAR (0,3 a 1,8) y 1,16 ± 0,38 logMAR (0,4 a 1,8), respectivamente (AU)

Introduction and objectives Age-related macular degeneration (AMD) is the primary cause of blindness in developed countries, particularly in older adults. Anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection is the current standard treatment for neovascular form of AMD. Studies reporting macular hole (MH) formation following anti-VEGF treatment are limited, and the exact pathogenesis is still under discussion. With the present study, we aim to analyse the clinical features of eyes developing MH after anti-VEGF therapy for neovascular AMD. Materials and methods Patients were treated with intravitreal anti-VEGF agents for at least one year and stable for at least six months. Best-corrected visual acuity (BCVA) and optical coherence tomography findings were evaluated. Results Nineteen eyes of 18 patients were included in this study. Patients had an average age of 77.7 years at first visit and eight were female. The average number of injections before the MH formation was four. MH developed after a mean follow-up of 5.1 months after the last injection. Sixteen eyes had (84.2%) had choroidal neovascular membrane without any abnormal vitreomacular traction. Eleven eyes (57.8%) had retinal pigment epithelium detachment (PED), two (10.5%) had an epiretinal membrane (ERM), and one (5.2%) had retinal pigment epithelium (RPE) tear. The mean first and last BCVA was 1.07 ± 0.48 LogMAR (0.3-1.8) and 1.16 ± 0.38 logMAR (0.4-1.8), respectively. Conclusions A macular hole can be observed in AMD patients receiving anti-VEGF therapy. Increased fibrovascular scar tissue due to subretinal fluid resolution, neovascular membrane contraction, and the presence of PED, RPE tear, and ERM may contribute to MH formation (AU)

[Choroidal thickness after scleral buckling surgery versus pars plana vitrectomy in macula-off rhegmatogenous retinal detachment]. / Aderhautdicke nach Buckelchirurgie versus Pars-plana-Vitrektomie bei Makula-off-rhegmatogener Ablatio retinae.

PURPOSE: Enhanced depth imaging (EDI) optical coherence tomography (OCT) provides high-definition cross-sectional images of the choroid. Information on alterations in choroidal thickness (CT) after scleral buckling surgery (SBS) and pars plana vitretomy (PPV) are rare. METHODS: The medical charts of 44 patients (44 eyes) who underwent SBS versus PPV for macula-off rhegmatogenous retinal detachment (RRD) were retrospectively analysed. Patients with a follow-up ≥ 6 months were included. Postoperative EDI-OCT images concerning CT were evaluated 1 week, 1 month and 6 months postoperatively in 2 groups: group 1: cerclage + cryopexy + subretinal fluid drainage (SRD) + SF6 or air (n = 28 eyes), group 2: PPV + laser photocoagulation + C3F8. Subfoveal CT was compared between the groups and with the non-operated fellow eye. RESULTS: Subfoveal CT in groups 1 and 2 was thicker 1 week postoperatively. There were no significant differences between the groups 2 or when comparing the operated eye with the fellow eye 1 and 6 months postoperatively. CONCLUSION: There were no differences in subfoveal CT 1 and 6 months after SBS between the eye with macula-off RRD and the fellow eye. Thicker CT 1 week postoperatively after SBS may most likely be induced by scleral buckle reduced blood flow and increased haemostasis in the choroidal circulation and by scleral and choroidal inflammation after cryopexy versus laser photocoagulation after SBS versus PPV.

[Choroidal thickness after scleral buckling surgery in macula-off rhegmatogenous retinal detachment]. / Aderhautdicke nach Buckelchirurgie bei Makula-off-rhegmatogener Ablatio retinae.

BACKGROUND: Enhanced depth imaging (EDI) optical coherence tomography (OCT) provides high-definition cross-sectional images of the choroid. Information on alterations in choroidal thickness (CT) after scleral buckling surgery (SBS) is rare. PATIENTS AND METHODS: The medical charts of 122 patients (122 eyes) who underwent SBS for macula-off rhegmatogenous retinal detachment (RRD) were retrospectively analyzed. Patients with a follow-up ≥ 6 months were included. Postoperative EDI-OCT images concerning CT were evaluated 1 week, 1 month and 6 months postoperatively in 4 groups: group 1 cerclage + cryopexy (n = 39 eyes), group 2 cerclage + cryopexy + sponge (n = 28 eyes), group 3 SBS + subretinal fluid drainage (SRD) (n = 25 eyes) and group 4 SBS + sponge + SRD (n = 30 eyes). Subfoveal CT was compared between the groups and with the non-operated fellow eye. RESULTS: Subfoveal CT in groups 1, 2, 3 and 4 was thicker 1 week postoperatively. There were no significant differences between the groups or when comparing the operated eye with the fellow eye 1 and 6 months postoperatively. CONCLUSION: There were no differences in subfoveal CT 1 and 6 months after SBS between the eye with macula-off RRD and the fellow eye. The use of a sponge or SRD induced no differences concerning subfoveal CT.

[Optical coherence tomography: anatomic and functional outcome after scleral buckling surgery in macula-off rhegmatogenous retinal detachment]. / OCT-, anatomische und funktionelle Ergebnisse nach Plombenchirurgie bei Macula-off rhegmatogener Ablatio retinae.

PURPOSE: The aim of this study was to evaluate results of optical coherence tomography (OCT) with regard to anatomic and functional outcome after scleral buckling surgery (SBS) in macula-off rhegmatogenous retinal detachment (RRD). METHODS: Medical charts of 87 patients (87 eyes), who underwent SBS for macula off RRD were analysed retrospectively. Patients with follow-up ≥ 6 months were included. Exclusion criteria were giant retinal tears, retinal dialysis, chorioretinal dystrophies, proliferative vitreoretinopathy ≥ grade-C1, schisis detachment and vitreous opacities. Reattachment success rate, pre- and postoperative visual acuity (VA) were examined. Postoperative spectral-domain (SD) OCT images were evaluated. The status of photoreceptor inner segment/outer segment (IS/OS) and external limiting memrane (ELM) junction were analysed. Potential risk factors influencing postoperative VA were evaluated by using linear multivariate logistic regression. RESULTS: The primary anatomic success rate was 93.8 % (81 eyes), final success rate was 98.7 % (86 eyes). Preserved ELM (OR 0.58, p = 0.004) and IS/OS integrity (OR 0.84, p = 0.031), drainage of subretinal fluid (OR 0.42, p < 0.0001) were detected as significant independent factors for influencing postoperative VA favourably. Duration of detachment > 6 days (OR 1.46, p = 0.04), two/three retinal breaks (OR 1.30, OR 1.36, p < 0.0001) were significant independent risk factors for a poor postoperative VA. Severe IS/OS disruption was the most important risk factor for poor postoperative VA (ß 0.724, OR 2.06, p < 0.0001). CONCLUSION: Severe IS/OS disruption may be the most important predictor of postoperative VA after successful surgery in macula-off rhegmatogenous retinal detachment.

Gaucher disease with communicating hydrocephalus and cardiac involvement.

A 14-year-old female with Gaucher disease presented with hydrocephalus, corneal opacities, cirrhosis, and cardiac valvular involvement. A homozygous D409H mutation was identified. She underwent surgery for aortic and mitral valve replacement. Because of severe calcification of the aortic root, no successful valve replacement was performed. She died on the third day after the explorative cardiac surgery. Cardiac abnormalities represent a life-threatening presentation of the homozygous D409H mutation. Identification of this type is essential prior to initiating appropriate therapy with enzyme replacement and cardiac corrective surgery.

Amyand's hernia: a series of 30 cases in children.

Amyand's hernia is a very rare condition with a presence of a vermiform appendix in an inguinal hernia sac. It is estimated to be found in approximately 1% of adult inguinal hernia. In this study, we report a retrospective analysis of 30 patients aged between 19 days and 8 years with an Amyand's hernia operated in our institution from 1998 to 2009, and we reviewed the literature on the topic. Hernia repair without an appendectomy was performed in patients with normal appendix. Emergency appendectomy through herniotomy was performed in cases of inflamed and perforated appendices.

[Papilloedema and brain abscess associated with isolated left superior vena cava draining in to the left atrium]. / Stauungspapille bei Gehirnabszess assoziiert mit isolierter persistierender linker Vena cava superior mit Drainage in den linken Vorhof.

BACKGROUND: Papilloedema and brain abscess associated with persistent left superior vena cava draining into the left atrium without sinus coronarius and atrium septum defect is rare and until now in only few cases have been reported. PATIENT: A 12 year-old girl was admitted because she had suffered from headache and blurred vision for 2 weeks. Fundus examination revealed papilloedema with peripapillary intraretinal haemorrhages. Pupillary reaction to light was normal. An afferent pupillary defect was negative. Neurological examination was without any focal neurological signs. Cerebral magnetic resonance imaging showed the characteristic features of a brain abscess in the left frontal lobe (3.5 x 3.0 x 2.8). Cardiological examination showed the presence of an isolated left superior vena cava draining into the left atrium in the absence of coronary sinus and atrial septum defect. CONCLUSION: Congenital heart disease such as LSVC is rare. The association of LSVC with papilloedema and brain abscess is very rarely seen. However, the complications of LSVC can be life-threatening. Therefore in children with papilloedema, intraocular and intraorbital reasons as well as congenital heart disease as the underlying reason should be included in the differential diagnosis.

[Hemicentral retinal artery occlusion associated with moyamoya syndrome]. / Hemizentralarterienverschluss bei Moyamoya-Syndrom.

Moyamoya syndrome is a rare cerebrovascular disorder characterized by bilateral progressive supraclinoidal stenosis or occlusion of the internal carotid artery and development of collateral vessels in the lenticulostriate region. The syndrome manifests itself in association with another disease or other clinical symptoms. We present the case of a 12-year-old girl with hemicentral retinal artery occlusion due to moyamoya syndrome associated with clinical and laboratory findings of presumed systemic lupus erythematosus.

Intravitreal triamcinolone acetonide for treatment of central retinal vein occlusion.

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide on visual acuity and intraocular pressure in patients with central retinal vein occlusion. METHODS: This prospective comparative non-randomized clinical interventional study included 32 patients (33 eyes) with central retinal vein occlusion. The study group (12 patients; 13 eyes) received an intravitreal injection of about 20 mg of triamcinolone acetonide. The control group (20 patients) did not receive any treatment. Mean follow-up was 10.1+/-8.6 months in the study group and 6.0+/-5.2 months in the control group. RESULTS: In the study group, mean visual acuity increased significantly (p=0.018) from 0.11+/-0.11 preoperatively to a best visual acuity during follow-up of 0.18+/-0.15. An improvement in visual acuity by at least 2 Snellen lines and 3 Snellen lines, respectively, was found for 8 (62%) eyes and 5 (38) eyes. Visual acuity measurements determined 1 month (p=0.038) and 3 months (p=0.046) after the injection were significantly higher than the baseline values. Increase in visual acuity was higher in the non-ischemic subgroup than in the ischemic subgroup. In the control group, baseline visual acuity and best visual acuity during the followup did not vary significantly (p=0.33). Visual acuity decreased significantly (p=0.007) towards the end of the follow-up. Comparing study group and control group, gain in visual acuity was significantly (p=0.01) higher in the study group. In the study group, intraocular pressure increased significantly (p=0.018) from 14.4+/-3.9 mmHg to a mean maximal value of 21.6+/-9.2 mmHg (range, 10-44 mmHg), and re-decreased (p=0.012) towards the end of follow-up to 15.3+/-5.1 mmHg (range, 10-21 mmHg). CONCLUSIONS: Intravitreal triamcinolone acetonide temporarily increases visual acuity in central retinal vein occlusion. It is accompanied by an increase in intraocular pressure.

[Are there predictors for proliferative retinopathy of prematurity and is supplemental oxygen a useful conservative treatment option?]. / Gibt es Prädiktoren für proliferierende Stadien der Retinopathia praematurorum und ist eine Sauerstoffsupplementation als konservative Therapiemöglichkeit sinnvoll? Eine Analyse anhand des eigenen Patientenguts.

BACKGROUND: Especially very immature preterm babies develop retinopathy of prematurity (ROP). This study aims at analysing risk factors for proliferative ROP and realizing the efficiency of supplemental oxygen therapy. PATIENTS: 180 preterm babies with birth weight < or = 1 500 grams were included retrospectively. METHODS: To determine potential predictors all preterm babies with ROP grade > or = 3 were matched to pairs with similar immature babies with ROP 1 or 2. Additionally we examined the influence of supplemental oxygen therapy on the coagulation rate of high grade retinopathy. RESULTS: 44 % of the preterm babies showed ROP. A longer duration of ventilation (21 vs. 33 days), a longer duration of oxygen supplementation (59 vs. 78 days), relapsing sepsis (10 vs. 19 babies with sepsis > 2 times), a large total volume of transfusions (median: 150 mL vs. 105 mL), chronic lung disease (CLD) (6 vs. 15 babies with oxygen requirements at 36 weeks post-menstrual age), a duration of intubation for more than 28 days (13 vs. 6 babies) and the lack of phototherapy (21 vs. 9 babies) were risk factors associated with ROP > or = 3 using univariate analysis [p < 0.05]. Only the both last criteria correlated with high grade ROP after logistic regression. The supplemental oxygen therapy showed no influence on the coagulation rate of high grade ROP. Possibly this therapy influences the frequency of surgical treatment of amotio- and of putting on a cerclage, but this remains still speculative because of the low case number. We saw no negative effect on the frequency of CLD and on the survival of the babies. CONCLUSIONS: Especially measures against long duration of intubation could help to prevent high grade ROP. The supplemental oxygen therapy may have a positive effect on course.

Diffuse diabetic macular oedema treated by intravitreal triamcinolone acetonide: a comparative, non-randomised study.

AIM: To report on visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide for treatment of diffuse diabetic macular oedema. METHODS: Prospective, comparative, non-randomised clinical interventional study included 136 patients with diffuse diabetic macular oedema. Patients of the study group (97 eyes) received an intravitreal injection of 20-25 mg of triamcinolone acetonide and no other retinal treatment. Patients of the control group (69 eyes) received focal or panretinal laser treatment if indicated. Mean (standard deviation) follow up was 8.4 (SD 6.0) months (range 1.03-25.2 months). RESULTS: Visual acuity (VA) increased significantly (p<0.001) in the study group with 66 (68%) eyes gaining in VA by at least two Snellen lines. In the control group, VA did not change significantly during the first 4 months of follow up, and decreased significantly (p<0.001) towards the end of the follow up. Difference in change of best VA was significant (p<0.001) between both groups. Correspondingly, the number of patients with VA improvement of two or more Snellen lines and visual loss of two or more Snellen lines, respectively, was significantly (p<0.001) higher and lower, respectively, in the study group. CONCLUSIONS: Intravitreal triamcinolone acetonide can temporarily increase VA in some patients with diffuse diabetic macular oedema.

Branch retinal vein occlusion treated by intravitreal triamcinolone acetonide.

PURPOSE: To evaluate the effect of intravitreal triamcinolone acetonide on visual acuity in branch retinal vein occlusion. METHODS: The prospective comparative nonrandomized clinical interventional study included 28 patients (28 eyes) with branch retinal vein occlusion. The study group consisting of 10 consecutive patients received an intravitreal injection of 20-25 mg of triamcinolone acetonide. The control group including 18 patients did not receive an intravitreal injection. The mean follow-up was 8.7+/-4.4 months. RESULTS: In the study group, mean visual acuity increased significantly (P=0.02) from 0.27+/-0.11 preoperatively to a best postoperative visual acuity of 0.45+/-0.27. Visual acuity measurements determined 1 month after the injection were significantly (P=0.027) higher than baseline values. Nine (90%) eyes gained in visual acuity, with six (60%) eyes showing an increase in visual acuity of at least two Snellen lines. In the ischaemic subgroup, visual acuity did not change significantly (0.18+/-0.18 to 0.13+/-0.04; P=0.66), while, in the nonischaemic subgroup, visual acuity increased significantly (P=0.012) from the baseline value to the best postoperative measurement (0.29+/-0.09 to 0.53+/-0.24). In the control group, baseline visual acuity and best visual acuity during the follow-up did not vary significantly (P=0.27). Comparing the study and control groups with each other, the gain in visual acuity was significantly higher in the study group at 1 month (P=0.016) and 2 months (P=0.012) after baseline. CONCLUSIONS: Intravitreal injection of triamcinolone acetonide can increase visual acuity in patients with branch retinal vein occlusion.

Exudative age-related macular degeneration treated by intravitreal triamcinolone acetonide. A prospective comparative nonrandomized study.

PURPOSE: To report on visual outcome of patients receiving an intravitreal injection of triamcinolone acetonide as treatment of progressive exudative age-related macular degeneration. METHODS: The prospective comparative nonrandomized clinical interventional study included 187 consecutive patients with progressive exudative age-related macular degeneration, divided into a study group of 115 patients receiving an intravitreal injection of 25 mg triamcinolone acetonide, and a control group of 72 patients without treatment. The mean follow-up was 6.0+/-4.2 months. RESULTS: Visual acuity increased significantly (P=0.03) in the study group, and decreased significantly (P=0.01) in the control group, at 1 month and 3 months after start of the study. Between the study group and control group, the differences in change of visual acuity were significant (P=0.001). In the study group, the number of patients with an increase in visual acuity of 2 or more Snellen lines was significantly (P=0.001) larger than in the control group. Correspondingly, the number of patients with a decrease of 2 or more Snellen lines was significantly (P=0.007) smaller in the study group. In all, 43 (37.4%) patients of the study group experienced an increase in best visual acuity by 2 or more Snellen lines. CONCLUSIONS: Visual acuity increased in patients with exudative age-related macular degeneration at 1 month and 3 months after an intravitreal injection of 25 mg triamcinolone acetonide.

Type 1 sirenomelia in one of male twins, with imperforate anus in the other male twin.

The etiology of sirenomelia sequence is still obscure. The role of maternal diabetes and a vascular steal phenomenon have been discussed [Gürakan et al. (1996) Turk J Pediatr 38:393-397]. Discordant monozygotic twin sirenomelia has been commonly reported but only rarely in dizygotic twins. The family of the presented twins had a high risk of diabetes mellitus. One of the twins has type 1 sirenomelia and the other had only an imperforate anus.

Basic, not acidic fibroblast growth factor stimulates proliferation of cultured human retinal pigment epithelial cells.

PURPOSE: In this study, we evaluated a possible effect of acidic and basic fibroblast growth factor (aFGF, bFGF) on the proliferation of human retinal pigment epithelial (RPE) cells in culture. As the RPE is the primary source for bFGF in the retina, such an effect would suggest autocrinic actions of FGFs. METHODS: Primary cultures of human and porcine RPE and an established human RPE cell line (D407) were subjected to aFGF and bFGF at different culture conditions. Cell proliferation was determined using the BrdU non-radioactive nucleotide analogue assay, and total protein was measured colorimetrically. The cells were subjected to aFGF and bFGF from 0.1 to 100 ng/ml for 1 to 14 days. RESULTS: In the presence of 100 ng/ml bFGF, cell proliferation doubled from day 2 (143+/-12 units) to day 6 (227+/-17). This effect was neither seen without bFGF nor with aFGF at the same concentration. The stimulating effect of bFGF on cell proliferation was dose-dependent, the ED50 being around 1-10 ng/ml. The bFGF effect was markedly greater at high fetal calf serum concentration (10% vs. 1%). No bFGF effect was seen on cells of the established human RPE cell line D407 nor on primary cultures from porcine RPE. CONCLUSIONS: bFGF, in contrast to its analogue aFGF, stimulates cell proliferation in cultured human RPE cells. It may act as an autocrinic agent (secretion by and action on the same cell) and thus be a specific regulator for cell proliferation in repair and replacement of the RPE cell monolayer.