Retinal Involvement Research Articles

Extramedullary Retinal Involvement in Chronic Myeloid Leukemia

Extramedullary Retinal Involvement in Chronic Myeloid Leukemia

Alzheimer's Disease Is Responsible for Progressive Age-Dependent Differential Expression of Various Protein Cascades in Retina of Mice.

Alzheimer's disease (AD) is a devastating neurodegenerative disease associated with cognitive impairments and memory loss usually in aged people. In the past few years, it has been detected in the eye retina, manifesting the systematic spread of the disease. This might be used for biomarker discovery for early detection and treatment of the disease. Here, we have described the proteomic alterations in retina of 2, 4, and 6 months old 3×Tg-AD mice by using iTRAQ (isobaric tags for relative and absolute quantification) proteomics technology. Out of the total identified proteins, 121 (71 up- and 50 down-regulated), 79 (51 up- and 28 down-regulated), and 153 (37 up- and 116 down-regulated) significantly differentially expressed proteins (DEPs) are found in 2, 4, and 6 month's mice retina (2, 4, and 6 M), respectively. Seventeen DEPs are found common in these three groups with consistent expression behavior or opposite expression in the three groups. Bioinformatics analysis of these DEPs highlighted their involvement in vital AD-related biological phenomenon. To further prompt the results, four proteins from 2 M group, three from 4 M, and four from 6 M age groups are successfully validated with Western blot analysis. This study confirms the retinal involvement of AD in the form of proteomic differences and further explains the protein-based molecular mechanisms, which might be a step toward biomarker discovery for early detection and treatment of the disease.

Peripapillary Versus Macular Combined Hamartoma of the Retina and Retinal Pigment Epithelium: Imaging Characteristics

To compare clinical, optical coherence tomography (OCT), and fundus autofluorescence (FAF) characteristics of peripapillary vs macular variants of combined hamartoma of the retina and retinal pigment epithelium (combined hamartoma). Retrospective observational, comparative case series. Setting: Multicenter collaborative study. Fifty eyes with a clinical diagnosis of combined hamartoma. Observational Analysis: A comparative analysis of color fundus photographs (CFPs), OCT, and FAF was performed for peripapillary and macular variants of combined hamartoma. Pigmentation and OCT features of macular and peripapillary combined hamartoma. The review of imaging from 50 eyes of 49 patients diagnosed with combined hamartoma identified 18 (36%) peripapillary lesions, 27 (54%) macular lesions, and 5 (10%) peripheral lesions. A comparative analysis of peripapillary vs macular combined hamartoma identified differences in the following features: lesion pigmentation on CFPs corresponding to hypoautofluorescent FAF (88% vs 0%, P < .001) and OCT features of full-thickness involvement (88% vs 3%, P < .001), preretinal fibrosis (27% vs 81%, P < .001), maxi peaks (5% vs 88%, P < .001), intraretinal cystoid spaces (72% vs 40%, P < .038), outer plexiform layer involvement (5% vs 96%, P < .001), ellipsoid zone disruption (83% vs 3%, P < .001), RPE disruption (77% vs 3%, P < .001), and choroidal neovascularization (16% vs 0%, P= .028). This comparative analysis identified a higher frequency of pigmentation with hypoautofluorescence, full-thickness retinal involvement, intraretinal cystoid spaces, ellipsoid zone disruption, RPE disruption, and choroidal neovascularization in peripapillary combined hamartoma. These findings suggest that lesions occurring near or at the optic nerve are associated with a more severe degree of pigmentary changes and retinal disruption than those located in the macula.

The ghost of the great imitator: prognostic factors for poor outcome in syphilitic uveitis

BackgroundSyphilitic uveitis is reemerging globally, may lead to any type of intraocular inflammation, and is potentially sight-threatening. We aim to characterize clinical features and prognostic factors in patients with syphilitic posterior uveitis.MethodsRetrospective chart review at two tertiary university-based referral centers in Brazil. Clinical data, laboratory results, and treatment outcomes were analyzed. Statistical analysis was performed using Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables.ResultsForty-four patients (81 eyes) were consecutively diagnosed with syphilitic posterior uveitis between March 2011 and April 2013.Thirty-one were male (70.5%) and the mean age was 43.8 years (range 15–81). HIV confection was disclosed in 12 patients (29.3%). The most prevalent finding was vitritis (85.2%), followed by retinal involvement (76.4%) and optic disc abnormalities (63.5%). After treatment, mean visual acuity improved from 1.2 (20/320) to 0.6 (20/80; median 20/30), but 19 eyes (23.5%) persisted with ≤ 1.0 (20/200). Factors associated with final visual acuity ≤ 1.0 despite therapy were prior use of systemic corticosteroids (p = 0.001), higher Venereal Disease Research Laboratory titers (p = 0.004), longer duration of symptoms (p = 0.024), and worse initial VA (p < 0.001).ConclusionsSyphilitic uveitis is reemerging. Delayed diagnosis and inadvertent use of systemic corticosteroids are potentially modifiable prognostic factors to be considered for possibly improving outcomes.

Phenotypic spectrum of autosomal recessive retinitis pigmentosa without posterior column ataxia caused by mutations in the FLVCR1 gene

Posterior column ataxia and retinitis pigmentosa (PCARP) is a rare form of syndromic RP associated with mutations in the FLVCR1 gene. Recent evidence has suggested a spectrum in the phenotype depending on the genotype. Six individuals with retinitis pigmentosa (RP) carrying mutations in the FLVCR1 gene underwent detailed ophthalmological examinations at the Center for Ophthalmology and two of these also an extensive neurological examination at the Department of Neurology in Tuebingen, Germany. The mutation spectrum in our cohort comprised one nonsense mutation, one 1-bp deletion, two missense variants, and one splice site variant (c.1092+5G>A). Three patients presented with a typical clinical picture of autosomal recessive RP, two patients presented with atypical RP, and one patient presented with a particularly mild form of RP. The findings of the patients that underwent detailed neurological and neurophysiological testing were not suggestive for the presence of progressive PCA, but one patient showed mild cerebellar signs without worsening over time. Five out of six of our cases carry the splice site variant c.1092+5G>A at least on one allele possibly providing evidence as to that this splice site variant may cause a milder form of non-syndromic autosomal recessive RP. Mutations in FLVCR1 can present with the clinical picture of a non-syndromic autosomal recessive RP (in this case RP without PCA), RP with mild cerebellar signs, but also PCARP. Additionally, we show evidence for a spectrum of the severity of the retinal involvement likely depending on the genotype.

Retinal involvement in an acute lymphoblastic leukemia.

We report a case of a patient who presents for ophthalmic complaints revealing systemic acute lymphoblastic leukemia. The eye fundus examination shows bilateral papilledema, retinal hemorrhages and diffuse white retinal infiltration. After chemotherapy, there was noticeable improvement of visual acuity and important regression of papilledema. Ocular involvement in leukemia is considered as a central nervous system lesion. It requires, therefore, a proper treatment including corticosteroids, chemotherapy and radiation treatment of the central nervous system.

Patterns of macular inner retinal layers involvement in eyes with optic nerve head drusen

Patterns of macular inner retinal layers involvement in eyes with optic nerve head drusen

Comparison of Retinal and Choroidal Involvement in Sarcoidosis-related Chorioretinitis Using Fluorescein and Indocyanine Green Angiography.

Comparison of Retinal and Choroidal Involvement in Sarcoidosis-related Chorioretinitis Using Fluorescein and Indocyanine Green Angiography.

Genetic Deciphering of Early-Onset and Severe Retinal Dystrophy Associated with Sensorineural Hearing Loss.

The specific association of Leber congenital amaurosis (LCA) or early-onset severe retinal dystrophy (LCA-like) with sensorineural hearing loss (SHL) is uncommon. Recently, we ascribed some of these distinctive associations to dominant and de novo mutations in the β-tubulin 4B isotype-encoding gene (TUBB4B), providing a link between a sensorineural disease and anomalies in microtubules behavior. Here, we report 12 sporadic cases with LCA/SHL or LCA-like/SHL and no TUBB4B mutation. Trio-based whole exome sequencing (WES) identified disease-causing mutations in 5/12 cases. Four out of five carried biallelic mutations in PEX1 (1/4) or PEX6 (3/4), involved in peroxisome biogenesis disorders from Zellweger syndrome characterized by severe neurologic and neurosensory dysfunctions, craniofacial abnormalities, and liver dysfunction to Heimler syndrome associating SHL, enamel hypoplasia of the secondary dentition, nail abnormalities, and occasional retinal disease. Upon reexamination, the index case carrying PEX1 mutations, a 4-year-old girl, presented additional symptoms consistent with Zellweger syndrome. Reexamination of individuals with PEX6 mutations (1/3 unavailable) revealed normal nails but enamel hypoplasia affecting one primary teeth in a 4-year-old girl and severe enamel hypoplasia of primary teeth hidden by dental prosthesis in a 50-year-old male, describing a novel PEX6-associated disease of the Zellweger/Heimler spectrum. Finally, hemizygosity for a CACNA1F mutation was identified in an 18-year-old male addressed for LCA/SHL, redirecting the retinal diagnosis to congenital stationary night blindness (CSNB2A). Consistent with the pure CSNB2A retinal involvement, SHL was ascribed to biallelic mutations in another gene, STRC, involved in nonprogressive DFNB16 deafness.

Swept-source optical coherence tomography and optical coherence tomography angiography in acquired toxoplasmic chorioretinitis: a case report

PurposeTo describe swept-source optical coherence tomography and optical coherence tomography angiography retinal changes in a case of acute toxoplasmic chorioretinitis both at the time of diagnosis and after healing.Case presentationA 57-year-old white woman suffering from acquired toxoplasmic chorioretinitis underwent swept-source optical coherence tomography and optical coherence tomography angiography both at the time of diagnosis and after healing. In the acute phase of the disease, swept-source optical coherence tomography clearly showed retinal and choroidal involvement in the superficial retina and in the choroidal swelling. Optical coherence tomography angiography showed a complete loss of deep and superficial capillary networks and of choroidal vessels in the area of the inflammation. After healing, swept-source optical coherence tomography showed a retinal thinning of the area involved, with a subversion of retinal layers and no visible change at the choroid level. On the other hand, optical coherence tomography angiography showed the persistence of a vascular occlusion at the retina and choroid level.ConclusionThis is the first case in the optical coherence tomography angiography literature that shows the imaging of toxoplasmic chorioretinal lesions. This case confirms the involvement of the retina and choroid in toxoplasmic uveitis and the disruptive potential of such inflammation. The optical coherence tomography angiography performed after healing showed a persistent ablation of the retina, choriocapillaris, and choroidal vessels. The non-invasive optical coherence tomography angiography imaging technique may have diagnostic and prognostic value in regard to toxoplasmic uveitis.

Diffuse Large B Cell Lymphoma in an Adolescent: A Challenging Case with Intracerebral and Retinal Involvement

Diffuse large B-cell lymphoma (DLBCL) is a rare lymphoma type in pediatric patients with usually good prognosis. We present the difficult diagnostic procedure and the complicated course in an adolescent patient with DLBCL.Case report: The 16-year-old female patient presented with a history of fever episodes during the past 3 weeks, hepatosplenomegaly, leukopenia, anemia, hypertriglyceridemia, massive hyperferritinemia and elevation of lactate dehydrogenase. Leukemia was excluded by bone marrow puncture. Initially, no significant lymph node enlargement was detected by imaging of the mediastinum and the abdomen but a pathological signal of the bone marrow could be observed in magnetic resonance imaging (MRI). Hemophagocytic lymphohistiocytosis (HLH) was diagnosed and the patient was treated with prednisone 0.5 mg/kg per day. The overall condition and the laboratory values improved but deteriorated on cessation of the steroid treatment. The result of the bone marrow biopsy then revealed an infiltration of a malignant B-cell lymphoma. Diagnosis of a DLBCL, Non-GCB-type with a BCL6-break was subsequently made in a biopsy of a lymphnode which had shown increased uptake in PET scan. Treatment according to the current NHL-BFM registry including administration of Rituximab was started. The course of disease was complicated by HLH symptoms with persistent fever and pancytopenia, renal failure, severe Methotrexate excretion failure requiring Carboxypeptidase treatment and Herpes virus encephalitis. After recovery progression of DLBCL was found and the treatment was switched to DA-EPOCH regimen and repeated systemic Rituximab administrations. Five months after diagnosis the girl suffered from visual impairment and convulsions. Ophthalmoscopy revealed retinal lesions and intracerebral lesions were detected by MRI but no abnormalities of cerebrospinal fluid (CSF) were found. Biopsy of a brain lesion confirmed cerebral involvement of DLBCL. Intensified treatment included high- dose steroids, cranio-spinal irradiation, high-dose Cytarabin and intrathecal Rituximab. Response of the cerebral lesions but no improvement of the visual impairment was found. Salvage treatment with Gemcitabin, Cisplatin and Rituximab was administered because of persistent nodal and extranodal lymphoma manifestations. The patient finally died due to refractory disease and severe bone marrow failure.Conclusion: This case of DLBCL in an adolescent girl is extraordinary in many ways. DLBCL, especially the non-GCB type, is a rare disorder in pediatric patients. Predominant bone-marrow involvement has been described in only few older patients with non-GCB-type DLBCL and mostly aggressive clinical course. HLH as a presenting feature is rather observed in T- or NK-cell lymphoma than in DLBCL. Finally, central nervous system (CNS) relapse occurs in only about 6% of adults with DLBCL regardless of CNS prophylaxis. Retinal and intraparenchymal CNS involvement without abnormalities in the CSF has been typically described for primary CNS lymphoma in adults. All these conditions have contributed to the adverse outcome in our patient. DisclosuresNo relevant conflicts of interest to declare.

Evaluation of Ocular Complications By Using Optical Coherence Tomography in Children with Sickle Cell Disease

Purpose: This study was aimed to evaluate ocular abnormalities by using optical coherence tomography (OCT) in children with sickle cell disease (SCD) and to search the relationship between OCT and clinical findings.Methods:The study included 108 eyes of 54 SCD patients as well as 110 eyes of 55 healthy subjects with no ocular pathology as a control group. A complete ophthalmologic examination was performed. Pupillary dilation was induced and macular sections were obtained with spectral domain OCT. Macular sections were evaluated according to the ETDRS map. Inner and outer retinal thicknesses were measured using the software in the device.Results:Foveal splaying, temporal thinning of retinal thickness, and vascular tortuosity were found to be significantly higher in the patient group than the control group (p <0.0001 for all three parameters)(Figure-1).The foveal diameter (1592.39 ± 175.56 μ) was significantly increased in the patient group compared to the control group (1391.01 ± 175.56 μ) (p<0.0001) and the foveal depth was significantly decreased in the patient group (121.15 ± 26.83 μ) compared to the control group (146.1 ± 12.25 μ) (p<0.0001). The mean total retinal thickness was 253.53 ± 22.31 μ in the patient group and 261.03 ± 18.48 μ in the control group and the difference was statistically significant (p = 0.007). Likewise, central retinal thickness was significantly decreased in the patient group (219.35 ± 10.53 μ) compared to the control group (235.32 ± 12.51 μ) (p <0.0001).Conclusions:Our study suggests that subclinical retinal involvement may occur in children with SCD. Foveal splaying, temporal thinning of retinal thickness, and vascular tortuosity are significant OCT findings in the children with SCD. It is seen that OCT is an important imaging method in addition to routine ophthalmologic examination to detecting ocular abnormalities in the early period and follow-up of this patient group.Keywords:Sickle Cell Disease, Childhood, Optical Coherence Tomography [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Spectrum of Newly Diagnosed Cytomegalovirus Retinitis in a Developing Country in the HAART Era

ABSTRACTPurpose: To characterize the presenting features of cytomegalovirus (CMV) retinitis in HIV-positive patients in a developing country in the HAART era.Methods: Retrospective chart review of all patients with CMV retinitis seen at a tertiary-care referral center between January 2006 to June 2017. Demographic and clinical data were collected to study the presenting features and risk factors for blindness.Results: Fifty-five patients with treatment-naïve CMV retinitis were enrolled; 75% were males. CD4 counts were below 50 cells/µL in 51.1%. Bilateral presentation was seen in 61.5%. Half (50.6%) of the eyes were blind at first examination. Zone 1 involvement was present in 46% of the eyes. Retinal area involvement > 25% was the only factor associated significantly with higher incidence of blindness (p = 0.016).Conclusions: There was extensive and bilateral presentation of CMV retinitis due to delayed presentation. Screening for CMV retinitis, irrespective of CD4 counts, may help in developing nations.

Distribution of the Extracellular Matrix in the Pararubral Area of the Rat

Previously we described similarities and differences in the organization and molecular composition of an aggrecan based extracellular matrix (ECM) in three precerebellar nuclei, the inferior olive, the prepositus hypoglossi nucleus and the red nucleus of the rat associated with their specific cytoarchitecture, connection and function in the vestibular system. The aim of present study is to map the ECM pattern in a mesencephalic precerebellar nucleus, the pararubral area, which has a unique function among the precerebellar nuclei with its retinal connection and involvement in the circadian rhythm regulation. Using histochemistry and immunohistochemistry we have described for the first time the presence of major ECM components, the hyaluronan, aggrecan, versican, neurocan, brevican, tenascin-R (TN-R), and the HAPLN1 link protein in the pararubral area. The most common form of the aggrecan based ECM was the diffuse network in the neuropil, but each type of the condensed forms was also recognizable. Characteristic perineuronal nets (PNNs) were only recognizable with Wisteria floribunda agglutinin (WFA) and aggrecan staining around some of the medium-sized neurons, whereas the small cells were rarely surrounded by a weakly stained PNNs. The moderate expression of key molecules of PNN, the hyaluronan (HA) and HAPLN1 suggests that the lesser stability of ECM assembly around the pararubral neurons may allow quicker response to the modified neuronal activity and contributes to the high level of plasticity in the vestibular system.

Retinopatía vasoproliferativa secundaria a enfermedad de Waldenström

A 66 year-old patient, monitored for diabetic retinopathy refractory to multiple treatment methods despite a good metabolic control, referred to progressive weight loss. For this reason, a systemic study was performed, detecting anaemia, elevation of the erythrocyte sedimentation rate, and hyperproteinaemia due to elevated serum levels of monoclonal IgM. Subsequently, by performing a bone marrow biopsy and genetic study, the diagnosis of Waldenström macroglobulinaemia was made.Waldenström's macroglobulinaemia is a low frequency lymphoproliferative disease, for which the main manifestation is a hyperviscosity syndrome that can produce ophthalmological signs detectable by funduscopy and imaging tests. A multimodal study is useful in the diagnosis and monitoring of retinal involvement. The incorporation of angiography by optical coherence tomography allows a more precise study of the microvascular disorders that may occur at the posterior pole level.

Persistent Fetal Vasculature With Elongated Ciliary Processes in Children

Outcomes and reoperation rates in infants with unilateral persistent fetal vasculature (PFV) with elongated or stretched ciliary processes have not been extensively studied and were excluded from the Infant Aphakia Treatment Study (IATS). The purpose of this study is to analyze the preoperative measurements, reoperation rates, and complications after surgery in unilateral anterior PFV with stretched processes. Retrospective case series. Inclusion criteria consisted of unilateral cataract surgery prior to 7months of age and anterior PFV with elongated ciliary processes. Eyes with posterior retinal involvement and less than 6months of follow-up were excluded. All patients underwent lensectomy, posterior capsulectomy, and vitrectomy. Eleven eyes of 11 patients were included. Patients had a mean age at surgery of 2.4 ± 1.4months. Average follow-up was 4.5 ± 3.7years. Globe axial lengths were 18.6 ± 1.9mm. Ten patients (91%) were initially left aphakic. Three patients (27%) later received a secondary intraocular lens (IOL), and 1 patient underwent an IOL exchange. Six out of 10 (60%) aphakic patients developed visual axis opacification. One aphakic patient required topical therapy for glaucoma. One additional patient developed neovascular glaucoma and retinal detachment. The eye was subsequently enucleated. Three patients underwent strabismus surgery. Two patients underwent pupilloplasty. Two patients (18.2%) had a final visual acuity better than 20/200. Eyes operated for PFV with elongated ciliary processes are unlikely to have a final visual acuity greater than 20/200 and many will need additional surgery. Postoperative visual axis opacification occurred in 60% and glaucoma developed in 18%.

Evaluation of retinal microvascular density in patients affected by systemic lupus erythematosus: an optical coherence tomography angiography study

Retinopathy in systemic lupus erythematosus (SLE) has an incidence of 7%–29% and is suggestive of high disease activity being a marker of poor visual outcome and prognosis for survival.1 Recently,...

Ultra-Wide Field Imaging Characteristics of Primary Retinal Vasculitis: Risk Factors for Retinal Neovascularization

ABSTRACTAim: To evaluate patterns of retinal vasculitis with ultra-wide field imaging (UWF) and ascertain the risk factors for retinal neovascularization.Methods: Consecutive patients of retinal vasculitis were included prospectively. Patients with retinal vasculitis secondary to uveitis were excluded. UWF was done for all the patients. Retinal involvement was classified into three zones and area of capillary non-perfusion was stratified into clock hours.Results: Two hundred patients were included, 85% (n = 170) were male. Mean age was 28.99 ± 10.56 years. Clinical examination revealed 65% cases (n = 130) to be bilateral, while UWF angiography detected 72.5% (n = 145) to have bilateral involvement. Retinal neovascularization was present in 47% (n = 188).Presence of posterior disease had very high odds ratio for development of retinal neovascularization as compared to cases restricted to retinal periphery (OR = 45.03, CI = 6.10–332.30, p = < 0.001).Conclusion: UWF imaging is useful in detecting retinal vasculitis, which is otherwise obscure to clinical examination and assessing risk factors for retinal neovascularization.

Electrophysiological function in eyes with reticular pseudodrusen according to fundus distribution.

Reticular pseudodrusen (RPD) could be present not only in the posterior pole but extramacular area also as a confluent morphological pattern. Thus RPD can be classified by the fundus distribution for the assessment of visual prognosis. The electrophysiological function in eyes with reticular pseudodrusen (RPD), showing various fundus distribution were evaluated using full-field electroretinogram (ERG). Retinal distribution of RPD was divided into three types (localized, intermediate, and diffuse) according to the extent of involvement of retinal areas by fundus photograph montages. RPD were present with the diffuse type in 21 eyes (25.6%), with the intermediate type in 30 eyes (36.6%), and with the localized type in 31 eyes (37.8%). The average age was 74.76 ± 4.52 (range, 65–81) years in the diffuse type, 72.47 ± 9.13 (range, 55–91) years in the intermediate type, and 70.26 ± 7.77 (range, 61–89) years in the localized type. The mean amplitudes of the scotopic rod response, scotopic maximal combined response, oscillatory potentials (OP), photopic cone response, and 30Hz cone flicker response were more decreased in the diffuse, intermediate, and localized types in order, except for the photopic cone a-wave response. The diffuse type showed reduced amplitudes of ERG responses than the normal control group under all testing conditions except for the photopic a-wave response, and differences were statistically significant with the age restriction and adjustment methods (Bonferroni-corrected P < 0.05). The mean implicit times of ERG responses were significantly delayed in the diffuse type in the photopic b-wave. (Bonferroni-corrected P < 0.05). Extensive retinal involvement of RPD correlates with severely reduced electrophysiological retinal function. This acquired form of decreased electrophysiological function should be regarded as different from those of hereditary retinal degeneration.

Detachment of retinal pigment epithelium in retinopathy due to malaria

Abstract Case report A 45-year-old man was diagnosed with malaria with neurological involvement. Two months later he referred metamorphopsia in the left eye. Malarial retinopathy was observed in the fundus examination. The Optic Coherence Tomography (OCT) of the macula showed parafoveal pigment epithelium detachment (DEP). Specific anti-malarial treatment was initiated, with the disappearance of the retinopathy being observed. Discussion Plasmodium falciparum is responsible for the retinopathy in neurological malaria. A funduscopic examination and macular OCT should be performed in these patients, as neurological malaria is associated with a higher mortality when there is a retinal involvement.