Scleral Thickness as a Risk Factor for Central Serous Chorioretinopathy and Pachychoroid Neovasculopathy.

In the pathophysiology of central serous chorioretinopathy (CSC), scleral changes inducing increased venous outflow resistance are hypothesized to be involved. This work aims to investigate anterior scleral thickness (AST) as a risk factor for pachychoroid disorders. A randomized prospective case-control study was performed at the Ludwig Maximilians University, Department of Ophthalmology. In patients with CSC or pachychoroid neovasculopathy (PNV) and in an age- and refraction-matched control group, swept source optical coherence tomography (SS-OCT) was used to measure anterior scleral thickness (AST). Subfoveal choroidal thickness (SFCT) was assessed using enhanced depth imaging OCT (EDI-OCT). In total, 46 eyes of 46 patients were included in this study, with 23 eyes in the CSC/PNV and 23 eyes in the control group. A significantly higher AST was found in the CSC/PNV compared with the control group (403.5 ± 68.6 (278 to 619) vs. 362.5 ± 62.6 (218 to 498) µm; p = 0.028). Moreover, the CSC/PNV group showed a higher SFCT (392.8 ± 92.8 (191-523) vs. 330.95 ± 116.5 (167-609) µm, p = 0.004). Compared with the age- and refraction-matched controls, patients with CSC and PNV showed a significantly thicker anterior sclera. Scleral thickness might contribute to the venous overload hypothesized to induce pachychoroid phenotypes.

Optical coherence tomography-based misdiagnosis and morphological distinction in pachychoroid neovasculopathy vs. polypoidal choroidal vasculopathy.

PURPOSE: To evaluate the rate of misdiagnosis of aneurysmatic pachychoroid type 1 choroidal neovascularization/polypoidal choroidal vasculopathy (PAT1/PCV) among cases diagnosed as non-aneurysmatic pachychoroid neovasculopathy (PNV) and to define optical coherence tomography (OCT) features facilitating their distinction. METHODS: The database of the Department of Ophthalmology, Ludwig-Maximilians University Munich, was screened for patients diagnosed with PNV. Multimodal imaging was screened for the presence of choroidal neovascularization (CNV) and aneurysms/polyps. Imaging features facilitating the diagnosis of PAT1/PCV were analysed. RESULTS: In total, 49 eyes of 44 patients with a clinical PNV diagnosis were included, of which 42 (85.7%) had PNV and 7 (14.3%) represented misdiagnosed PAT1/PCV. SFCT was comparable (PNV: 377 ± 92 vs. PAT1/PCV: 400 ± 83 µm; p = 0.39). Whereas no difference was detected in total pigment epithelium detachment (PED) diameter (p = 0.46), maximum PED height was significantly higher in the PAT1/PCV group (199 ± 31 vs. 82 ± 46, p < 0.00001). In a receiver operating characteristic (ROC) analysis, the optimum cutoff for defining "peaking PED" was 158 µm with an area under the curve of 0.969, a sensitivity of 1.0 (95% CI: 0.59-1.0), and a specificity of 0.95 (95% CI: 0.84-0.99). Sub-retinal hyperreflective material (SHRM; p = 0.04), sub-retinal ring-like structures (SRRLS; p < 0.00001), and sub-RPE fluid (p = 0.04) were significantly more frequent in eyes with PAT1/PCV. CONCLUSION: A relevant percentage of eyes diagnosed with PNV might instead suffer from PAT1/PCV. The detection of a maximum PED height ("peaking PED") exceeding approximately 150 µm, SHRM, SRRLS, and sub-RPE fluid might greatly aid in the production of a more accurate diagnosis.

Posterior Segment Involvement in Infantile Nephropathic Cystinosis - A Review.

Cystinosis is a rare lysosomal storage disease with a prevalence of 1 : 100 000 - 1 : 200 000 cases. It is caused by biallelic mutations in the CTNS gene, which encodes cystinosin, that transport cystine out of the lysosomes. Due to its dysfunction, cystine crystals accumulate in the lysosomes and ultimately cause apoptosis of the cell. Since cystinosin is ubiquitously present in the body, cystine crystals are deposited in every body structure and lead to the dysfunction of various organ systems in the course of time. Cystine crystals deposited in the cornea are a clinical hallmark of the disease, while there is less awareness of concomitant posterior segment alterations. Symmetrical pigment epithelial mottling and patches of depigmentation frequently start in the periphery and progress towards the posterior pole and can be encountered upon fundus biomicroscopy. Spectral-domain optical coherence tomography (SD-OCT) is an elegant tool for visualizing chorioretinal cystine crystals at the posterior pole. An SD-OCT-based clinical grading of the severity of the chorioretinal manifestation can potentially be applied as a biomarker for systemic disease status and for monitoring oral therapy adherence in the future. Along with previous histological examinations, it may also give information about the location of cystine crystals in the choroid and retina. This review aims to increase the awareness of vision-threatening retinal and choroidal changes in cystinosis and the concomitant findings in SD-OCT.

Long-Term Results of Adjunct Autologous Platelet-Rich Plasma in Lamellar Macular Hole Surgery Showing Lasting Restoration of Foveal Anatomy.

The aim of this study was to evaluate the long-time results of highly concentrated autologous platelet-rich plasma (PRP) used as an adjunct in lamellar macular hole (LMH) surgery. Nineteen eyes of nineteen patients with progressive LMH were enrolled in this interventional case series, on which 23/25-gauge pars plana vitrectomy was performed and 0.1 mL of highly concentrated autologous platelet-rich plasma was applied under air tamponade. Posterior vitreous detachment was induced, and the peeling of tractive epiretinal membranes, whenever present, was performed. In cases of phakic lens status, combined surgery was carried out. Postoperatively, all patients were instructed to remain in a supine position for the first two postoperative hours. Best-corrected visual acuity (BCVA) testing, microperimetry, and spectral domain optical coherence tomography (SD-OCT) were carried out preoperatively and at minimum 6 months (in median 12 months) postoperatively. Foveal configuration was postoperatively restored in 19 of 19 patients. Two patients who had not undergone ILM peeling showed a recurring defect at 6-month follow-up. Best-corrected visual acuity improved significantly from 0.29 ± 0.08 to 0.14 ± 0.13 logMAR (p = 0.028, Wilcoxon signed-rank test). Microperimetry remained unchanged (23.38 ± 2.53 preoperatively; 23.0 ± 2.49 dB postoperatively; p = 0.67). No patients experienced vision loss after surgery, and no significant intra- or postoperative complications were observed. Using PRP as an adjunct in macular hole surgery significantly improves morphological and functional outcomes. Additionally, it might be an effective prophylaxis to further progression and also the formation of a secondary full-thickness macular hole. The results of this study might contribute to a paradigm shift in macular hole surgery towards early intervention.

Corneal Manifestation in Patients with Infantile Nephropathic Cystinosis.

Nephropathic cystinosis is a rare autosomal recessive disease caused by mutations in the CTNS gene. This causes dysfunction of cystinosin, a protein that transports cystine out of lysosomes, causing cystine crystals to accumulate in cells in most organ systems. While renal complications predominate in the early forms of cystinosis, corneal crystal accumulation will inevitably manifest in all patients. The main symptoms are photophobia along with glare sensitivity and blepharospasm. In addition, corneal crystal accumulation can cause other complications, such as recurrent corneal erosions, punctate or filamentary keratopathy, and chronic dry eye. Eventually, peripheral corneal neovascularization and limbal stem cell deficiency may develop. Ophthalmologists play a key role in the early diagnosis of patients with cystinosis. This review aims to not only raise awareness of secondary complications of corneal crystal accumulation, but also to highlight current treatment options and challenges that ophthalmologists and pediatricians might face.

Spectral domain optical coherence tomography-based retinochoroidal cystine crystal score: a window into infantile nephropathic cystinosis.

PRÉCIS: Cystinosis is a lysosomal storage disease leading to an accumulation of cystine crystals in several organs. We aim to comprehensively describe chorioretinal cystine crystals via spectral domain optical coherence tomography (SD-OCT) and elaborate a new biomarker for systemic disease control. BACKGROUND/AIMS: Cystinosis is a rare lysosomal storage disease leading to an accumulation of cystine crystals in several organs. This study aims to describe the deposition of retinochoroidal crystals in infantile nephropathic cystinosis and to elucidate their potential value as an objective biomarker for systemic disease control. METHODS: This cross-sectional study was carried out by the University Eye Hospital of the Ludwig-Maximilian University (Munich, Germany) in collaboration with the German Cystinosis Study Group. A complete ophthalmologic examination was performed, along with posterior segment SD-OCT (Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany). Retinochoroidal crystals were graded by employing a novel semiquantitative grading system-the retinochoroidal cystine crystal score (RCCCS). To quantify quality of vision, patients completed a specific questionnaire. A total of 85 eyes of 43 patients with cystinosis were included (mean age 22.3±8.8 years, range 6-39; male:female ratio=23:20). RESULTS: Cystine crystals were detectable in all neuroretinal layers and the choroid, most frequently in the choriocapillaris. The RCCCS was negatively correlated with cysteamine intake (r=0.533, p=0.001) and positively with cystatin C, a stable parameter of renal function (r=0.496, p=0.016). Moreover, the value of the RCCCS affected subjective quality of vision. Genetic analysis indicated pronounced crystal deposition in patients with heterozygous mutations containing the 57-kb-deletion allele of the CTNS gene. CONCLUSION: Ocular cystinosis leads to retinochoroidal crystal accumulation in every stage of the disease. Crystal deposition may be markedly influenced by oral cysteamine therapy. Therefore, the presented SD-OCT based grading system might serve as an objective biomarker for systemic disease control.

Progression of Pachychoroid Neovasculopathy into Aneurysmal Type 1 Choroidal Neovascularization or Polypoidal Choroidal Vasculopathy.

PURPOSE: To describe the progression of pachychoroid neovasculopathy (PNV) into pachychoroid aneurysmal type 1 choroidal neovascularization (PAT1)/polypoidal choroidal vasculopathy (PCV). DESIGN: Retrospective longitudinal cohort study. SUBJECTS: Patients diagnosed with PNV with a follow-up of ≥2 years. METHODS: Multimodal imaging, including OCT and fluorescein and indocyanine green angiography, was reviewed for the presence of choroidal neovascularization (CNV), aneurysms within/at the margins of the CNV, and subfoveal choroidal thickness (SFCT). MAIN OUTCOME MEASURES: Rate of PNV to PAT1/PCV conversion and risk factors thereof. RESULTS: In total, 37 eyes of 32 patients with PNV with a mean follow-up of 3.3 ± 1.1 years (range, 2.0-5.2) were included in the study. At PNV diagnosis, the mean age was 59.7 ± 8.7 years (range, 38.5-78.0 years) and mean SFCT was 357 ± 92 µm (185-589). During the follow-up, 5 (13.5%) eyes developed aneurysms after a mean 3.4 ± 0.8 years (2.3-4.2), defining PAT1/PCV. The risk of PAT1/PCV conversion was 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. A mean of 5.2 ± 4.0 to 7.9 ± 3.6 intravitreal anti-VEGF injections were given per year, resulting in a significant reduction of SFCT to 317 ± 104 µm (122-589) (P = 0.0007). The age at diagnosis of PNV was significantly lower in eyes that later went on to develop PAT1/PCV (54.0 ± 5.6 [45.9-60.5] vs. 61.2 ± 8.4 [38.5-78.0] years; P = 0.025). At the end of the follow-up, SFCT had on average decreased by -14.0% ± 17.6% (-55.9% to 23.1%) in the PNV group, whereas it had increased by mean 6.9% ± 4.4% (0.00%-10.8%) in the PAT1/PCV conversion group (P = 0.0025). CONCLUSIONS: PNV can develop aneurysms within its type 1 CNV, defining the conversion to PAT1/PCV. In this study, the conversion to PAT1/PCV was seen in 13.5% of eyes, resulting in Kaplan-Meier estimates of risk for conversion of 7.4% at year 3, 13.6% at year 4, and 30.7% at year 5. Younger age at diagnosis of PNV and sustained choroidal thickening despite anti-VEGF therapy might be risk factors for PNV to progress into PAT1/PCV.

Pachychoroid disease and its association with retinal vein occlusion: a case-control study.

The development of a retinal vein occlusion (RVO) is multifactorial. This study investigates pachychoroid as a risk factor for RVO or as an entity sharing common pathophysiology with RVO. A database screening at the University Eye Hospital, Ludwig-Maximilian University Munich, Germany was performed for patients diagnosed with central or branch RVO (CRVO/BRVO). In every patient a complete ophthalmologic examination was performed, including posterior segment enhanced depth spectral domain optical coherence tomography (EDI-SD-OCT). The SD-OCT scans of respective partner eyes without history of RVO were compared to an age- and refraction-matched, randomly recruited normal control group. In total, 312 eyes of 312 patients were included in this study, with 162 eyes in the RVO and 150 eyes in the control group. A significantly higher subfoveal choroidal thickness (SFCT) was found in the RVO (310.3 ± 72.5 (94 to 583) µm) as compared to the control group (237.0 ± 99.0 (62 to 498); p < 0.00001). Moreover, the RVO group showed a significantly higher prevalence of a symptomatic pachychoroid (22 vs. 9 eyes; odds ratio: 2.46; 95 CI: 1.10 to 5.53; p = 0.029). Since pachychoroid disease represents a bilateral entity, it might be a risk factor for RVO, or share risk factors with RVO.

Migraine attacks as a result of hypothalamic loss of control.

Migraine is a complex neurological disorder affecting approximately 12% of the population. The pathophysiology is not yet fully understood, however the clinical features of the disease, such as the cyclic behaviour of attacks and vegetative symptoms, suggest a prominent role of the hypothalamus. Previous research has observed neuronal alterations at different time points during the migraine interval, specifically just before the headache is initiated. We therefore aimed to assess the trajectory of migraineurs' brain activity over an entire migraine cycle. Using functional magnetic resonance imaging (fMRI) with pseudo-continuous arterial spin labelling (ASL), we designed a longitudinal intra-individual study to detect the rhythmicity of (1) the cerebral perfusion and (2) the hypothalamic connectivity over an entire migraine cycle. Twelve episodic migraine patients were examined in 82 sessions during spontaneous headache attacks with follow-up recordings towards the next attack. We detected cyclic changes of brain perfusion in the limbic circuit (insula and nucleus accumbens), with the highest perfusion during the headache attack. In addition, we found an increase of hypothalamic connectivity to the limbic system over the interictal interval towards the attack, then collapsing during the headache phase. The present data provide strong evidence for the predominant role of the hypothalamus in generating migraine attacks. Due to a genetically-determined cortical hyperexcitability, migraineurs are most likely characterised by an increased susceptibility of limbic neurons to the known migraine trigger. The hypothalamus as a metronome of internal processes is suggested to control these limbic circuits: migraine attacks may occur as a result of the hypothalamus losing control over the limbic system. Repetitive psychosocial stress, one of the leading trigger factors reported by patients, might make the limbic system even more vulnerable and lead to a premature triggering of a migraine attack. Potential therapeutic interventions are therefore suggested to strengthen limbic circuits with dedicated medication or psychological approaches.

Vanishing pachy-choroid in pachychoroid neovasculopathy under long-term anti-vascular endothelial growth factor therapy.

BACKGROUND: To investigate the diagnostic value of choroidal thickness in the definition of pachychoroid neovasculopathy (PNV), especially in eyes treated with anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Twenty-two consecutive eyes of 11 patients with uni- or bilateral PNV were analyzed. Anti-VEGF treatment was correlated with changes in choroidal thickness on enhanced depth imaging optical coherence tomography. RESULTS: There were 14 eyes with PNV and 8 non-neovascular partner eyes. Mean age was 64.2 ± 4.0 (range: 60-72), total follow-up was 1.8 ± 0.4 (1-2) years. In PNV eyes, choroidal thickness at baseline was 400 ± 58 (269-485) µm. After two years and 13 anti-VEGF injections on average, a mean reduction of - 39 ± 10 (- 26 to - 56) % to final 241 ± 52 (162-327) µm was observed (p < 0.0001). Meanwhile, choroidal thickness in the partner eyes remained stable (p > 0.13 for all comparisons). A significant correlation of choroidal thinning and anti-VEGF injection rate was observed at year one (r = - 0.79; R2 = 0.63; p = 0.00073) and two (r = - 0.69; R2 = 0.48; p = 0.019). While 85.7% of PNV eyes exceeded a pachychoroid threshold of ≥350 µm at baseline, this figure dropped to 21.4% at year one and 0% at year two. CONCLUSION: In PNV, choroidal thickness significantly decreases with anti-VEGF therapy, resembling a "vanishing pachy-choroid", and thus does not represent a valid long-term diagnostic criterium, especially when differentiating PNV from nAMD.

Subthreshold laser therapy with a standardized macular treatment pattern in chronic central serous chorioretinopathy.

PURPOSE: There is an ongoing controversial debate about the effectiveness of laser treatments in chronic central serous chorioretinopathy (cCSC). We performed a prospective non-randomized interventional study to learn about the effects of a subthreshold laser treatment (Topcon Endpoint Management™, Topcon Healthcare Inc., Tokyo, Japan) in patients with cCSC. METHODS: Patients with cCSC and a minimum symptom duration of 4 months were included and treated with a standardized laser pattern covering the macular area. Retreatment was performed every 3 months if persistent subretinal fluid was observed. The primary endpoint was resolution of subretinal fluid at 6 months. Further outcome parameters included best corrected visual acuity, microperimetry, central macular and subfoveal choroidal thickness. RESULTS: A total of 42 eyes of 39 patients were included. Mean patient age was 48 ± 10.6 years (range 25-67). Mean symptomatic time before inclusion into the study was 134 ± 133.4 weeks (16-518). Before inclusion, 78.6% of the patients had failed to resolve subretinal fluid under mineralocorticoid receptor antagonists and 14.3% had a recurrence after half-dose photodynamic therapy. Complete resolution of subretinal fluid was observed in 42.9% at 6 months and in 53.8% at 12 months after baseline. Central retinal thickness decreased from 398 ± 135 µm to 291 ± 68 µm (p < 0.001), subfoveal choroidal thickness changed slightly (430 ± 116 µm to 419 ± 113 µm, p = 0.026), microperimetry-derived macular function improved by 19.1 ± 4.7 dB to 21.3 ± 4.8 dB (p = 0.008) and mean BCVA improved by 4.9 ± 8.6 ETDRS letters (p < 0.001). CONCLUSION: The results show that the investigated laser treatment is effective in reducing subretinal fluid and leads to an improvement of functional parameters.

Pachychoroid Neovasculopathy Disguising as Age-Related Macular Degeneration Treated by Spironolactone and Anti-VEGF Combination Therapy.

Nonresponse of neovascular age-related macular degeneration (nAMD) to anti-vascular endothelial growth factor (anti-VEGF) therapy can often be attributed to misdiagnosis, and pathologies mimicking AMD might require different therapeutic concepts. In the following, we want to outline a case of presumed nAMD which revealed to be pachychoroid neovasculopathy (PNV) and was successfully treated by the addition of spironolactone. A 67-year-old female patient was referred for nonresponse of nAMD on her left eye after 29 intravitreal injections of aflibercept with no complete resolution of subretinal fluid. On fundoscopy, both maculae presented with pigment epithelium alterations, while the left eye showed subretinal fluid on optical coherence tomography (OCT) with an associated pigment epithelium detachment, which revealed to contain a neovascular network on OCT angiography. There was faint leakage on fluorescence (FAG) and indocyanine green angiography (ICGA) and some focal vascular dilation of the neovascular network on ICGA. Due to the absence of Drusen on any eye, a thick choroid, and the presence of a gravitational tract on blue autofluorescence (BAF), chronic central serous chorioretinopathy with a choroidal neovascularization, defined as PNV in the pachychoroid disease was diagnosed. Upon the addition of spironolactone to anti-VEGF treatment, choroidal thickness significantly decreased, and subretinal fluid resolution was observed and maintained for the first time. In conclusion, PNV should be ruled out in cases of presumed nAMD nonresponding to anti-VEGF. In these cases, a combination therapy of anti-VEGF and mineralocorticoid antagonists can facilitate fluid resorption.

Visual outcome after rhegmatogenous retinal detachment repair surgery in patients with multifocal vs monofocal intraocular lenses.

PURPOSE: To evaluate functional outcome after retinal detachment (RD) repair surgery in eyes with a multifocal intraocular lens (mIOL). SETTING: Ludwig-Maximilians-University, Munich, Germany. DESIGN: Single-center case control study. METHODS: 52 pseudophakic eyes with successful anatomical outcome after surgical RD repair were included. Retrospectively, 21 mIOL eyes were compared with a matched group of 21 monofocal eyes over 6 weeks. Prospectively, corrected distance visual acuity (CDVA) was evaluated over 12 months in these eyes. Furthermore, uncorrected distance, intermediate, and near visual acuity (UDVA, UIVA, and UNVA, respectively), defocus curves, and patient-reported outcomes were evaluated at 1 year in 24 mIOL eyes. RESULTS: 52 eyes of 48 patients comprised the study. The mean CDVA (logMAR) improved significantly from 1.35 ± 1.38 to 0.29 ± 0.37 at 6 weeks and remained stable at 12 months postoperatively in monofocal eyes (P = .001) and from 1.16 ± 1.2 to 0.37 ± 0.29 (6 weeks) and 0.20 ± 0.36 (12 months) in mIOL eyes (P = .001). Univariate factorial analysis of variance showed no statistically significant differences in CDVA at 6 weeks or 12 months postoperatively for IOL type or for preoperative macular status (P > .05). In the prospective cohort of 24 mIOL eyes, a mean CDVA of 0.13 ± 0.33 logMAR, UDVA of 0.21 ± 0.34 logMAR, UIVA of 0.17 ± 0.28 logMAR, and UNVA of 0.23 ± 0.32 logMAR was achieved. Macular status did not affect final outcome significantly (P > .05). Most patients stated they usually did not need spectacles; no patient wanted mIOL replacement. CONCLUSIONS: 1 year after successful anatomical repair after 23-gauge vitrectomy with gas tamponade, functionality of mIOL was restored, and CDVA was comparable with that of patients with monofocal IOL.

Establishing an objective biomarker for corneal cystinosis using a threshold-based Spectral domain optical coherence tomography imaging algorithm.

PURPOSE: The purpose of the present study was to establish a semi-automated threshold-based image segmentation algorithm to detect and objectively quantify corneal cystine crystal deposition in ocular cystinosis with anterior segment optical coherence tomography (AS-OCT). METHODS: This prospective, observational, comparative study included 88 eyes of 45 patients from the German Cystinosis Registry Study as well as 68 eyes of 35 healthy control subjects. All eyes were imaged with AS-OCT (Cirrus HD-OCT 5000, Carl Zeiss Meditec AG, Jena, Germany). As an initial step, B-scan images were subjectively analysed for typical changes in morphology in comparison to healthy controls. Based on the experience gained, an objective semi-automated B-scan image segmentation algorithm was developed using a grey scale value-based threshold method to automatically quantify corneal crystals. RESULTS: On AS-OCT B-scans, corneal crystals appeared as hyperreflective deposits within the corneal stroma. The crystals were distributed either in all stromal layers (43 eyes, 49%) or confined to the anterior (23 eyes, 26%) or posterior stroma (22 eyes, 25%), respectively. The novel automatic B-scan image segmentation algorithm was most efficient in delineating corneal crystals at higher grey scale thresholds (e.g. 226 of a maximum of 255). Significant differences in suprathreshold grey scale pixels were observable between cystinosis patients and healthy controls (p < 0.001). In addition, the algorithm was able to detect an age-dependent depth distribution profile of crystal deposition. CONCLUSION: Objective quantification of corneal cystine crystal deposition is feasible with AS-OCT and can serve as a novel biomarker for ocular disease control and topical treatment monitoring.

Biotinidase deficiency: A treatable cause of hereditary spastic paraparesis.

OBJECTIVE: To expand the genetic spectrum of hereditary spastic paraparesis by a treatable condition and to evaluate the therapeutic effects of biotin supplementation in an adult patient with biotinidase deficiency (BD). METHODS: We performed exome sequencing (ES) in a patient with the clinical diagnosis of complex hereditary spastic paraparesis. The patient was examined neurologically, including functional rating scales. We performed ophthalmologic examinations and metabolic testing. RESULTS: A 41-year-old patient presented with slowly progressive lower limb spasticity combined with optic atrophy. He was clinically diagnosed with complex hereditary spastic paraparesis. The initial panel diagnostics did not reveal the disease-causing variant; therefore, ES was performed. ES revealed biallelic pathogenic variants in the BTD gene leading to the genetic diagnosis of BD. BD is an autosomal recessive metabolic disorder causing a broad spectrum of neurologic symptoms, optic atrophy, and dermatologic abnormalities. When treatment is initiated in time, symptoms can be prevented or reversed by biotin supplementation. After diagnosis in our patient, biotin supplementation was started. One year after the onset of therapy, symptoms remained stable with slight improvement of sensory deficits. CONCLUSIONS: These findings expand the genetic spectrum of the clinical diagnosis of complex hereditary spastic paraparesis by a treatable disease. Today, most children with BD should have been identified via newborn screening to start biotin supplementation before the onset of symptoms. However, adult patients and those born in countries without newborn screening programs for BD are at risk of being missed. Therapeutic success depends on early diagnosis and presymptomatic treatment.

Ranibizumab non-response in pachychoroid neovasculopathy: Effects of switching to aflibercept.

Non-response to intravitreal ranibizumab represents a frequent problem in pachychoroid neovasculopathy (PNV). To investigate the effectivity of switching to aflibercept, the database of the Ludwig Maximilians University, Munich, was screened for patients fulfilling the following inclusion criteria: (i) diagnosis of PNV; (ii) inadequate response to ≥ 3 ranibizumab injections, in spite of monthly dosing, defined as persistence of subretinal-fluid four weeks after the last ranibizumab injection; (iii) resulting switch to aflibercept administered as three monthly injections. Primary outcome measure was percentage of eyes with a dry macula four weeks after the third aflibercept injection. Secondary outcome measures included changes in maximum subretinal fluid (SRF), central subfield thickness (CST) and subfoveal choroidal thickness (SFCT). In total, 14 eyes of 14 patients were included. Mean age was 64.1 ± 7.5 (range: 51-78) years. Switching to aflibercept was performed after mean 8.4 ± 4.1 (3-15) ranibizumab injections. While no eye (0%) achieved a dry macula status during ranibizumab treatment, switching to aflibercept achieved a dry macula status in eight eyes (57.1%) after three injections. While both ranibizumab and aflibercept showed an effect on CST (p = 0.027, p = 0.003), only aflibercept showed a significant effect on SRF (p = 0.0009) and SFCT (p = 0.044). In cases of PNV not responding to intravitreal ranibizumab, switching treatment to aflibercept induces a favorable short-term response resolving persistent fluid and achieving a dry macula. Further studies with longer follow-up are warranted.

Response of neovascular central serous chorioretinopathy to an extended upload of anti-VEGF agents.

PURPOSE: To determine the anatomical and functional outcomes of an extended 6-month intravitreal anti-vascular endothelial growth factor (anti-VEGF) upload in choroidal neovascularization (CNV) secondary to chronic central serous chorioretinopathy (CSCR). METHODS: A retrospective database analysis was performed applying the following inclusion criteria: (1) diagnosis of CSCR, (2) diagnosis of secondary CNV, and (3) treatment of at least six consecutive injections of anti-VEGF. Outcome measures included the change of central retinal subfield thickness, remodeling of the pigment epithelium detachments, and change in visual function. RESULTS: Twenty-one eyes of 21 patients were included. Mean patient age was 65 ± 8.3 years, and 35% of the patients (n = 8) were female. Mean disease duration before diagnosis of CNV was 48 ± 25.3 months. Mean central retinal thickness decreased from 346 ± 61 to 257 ± 57 µm (p < 0.01) after the sixth injection while mean visual acuity improved from 0.65 ± 0.35 to 0.49 ± 0.29 (logMAR; p < 0.01). Of note, an extended upload of six as opposed to three injections yielded an additional mean central retinal thickness reduction (280 ± 46 µm vs. 257 ± 57 µm, p = 0.038). Significant CNV remodeling was observed as a decrease in pigment epithelium detachment (PED) vertical (p = 0.021) and horizontal diameter (p = 0.024) as well as PED height (p < 0.01). CONCLUSION: An extended anti-VEGF upload of six consecutive injections seems to be effective in inducing CNV remodeling and fluid resorption in CNV complicating chronic CSCR.