Macular hypoplasia and high myopia in 48, xxyy syndrome: a unique case of 48, xxyy syndrome that presents with high myopia and macular dysplasia.

BACKGROUND: Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease. CASE PRESENTATION: A 6-year-old boy, who had been experiencing progressive vision deterioration in both eyes for the past two years, presented with a history of poor vision, delayed motor skills. The patient was diagnosed with micropenis in the pediatric outpatient clinic. Sparse hair, an unusually tall stature and craniofacial dysmorphology characterized by ocular hypertelorism, depressed nasal bridge, and epicanthic folds were observed. Comprehensive ophthalmic examination revealed high myopia and grade 3 macular hypoplasia. Diagnostic investigations including karyotype analysis and whole-exome sequencing identified an anomalous male karyotype comprising two X and two Y chromosomes, confirming a diagnosis of 48, XXYY syndrome. CONCLUSIONS: This study underscores the rare association of high myopia and grade 3 macular dysplasia with 48, XXYY syndrome. To our knowledge, this case marks the first recorded instance of macular dysplasia in a patient with 48, XXYY syndrome. This novel finding enhances our understanding of this syndrome's phenotypic variability.

Choroid cavitation associated with macular coloboma. Multimodal study. Image en face.

Intrachoroidal cavitation is a finding identified with OCT initially described in myopic patients, it also appears in non-myopic patients. It can occur in both the peripapillary area and the posterior pole. Macular coloboma is a defect of embryonic development of the posterior pole, in structural OCT the absence of the retinal pigment epithelium and choroidal vessels is essential. In this case, intrachoroidal cavitation circumscribes the macular coloboma, in the absence of an intercalary membrane. The en face image allows us to assess the relationship between the two structures as well as their magnitude.

Intercalary membrane break and detachment causes intrachoroidal cavitation in macular coloboma.

PURPOSE: To describe the clinical and imaging features in a series of patients diagnosed with macular coloboma (MC) and intrachoroidal cavitation (ICC). METHODS: Patients diagnosed with MC based on clinical examination between June 2017 and July 2021 were retrieved from the electronic medical record system and were included in the study. Colour fundus photographs, optical coherence tomography (OCT) and Multicolour® imaging scans of these patients were analysed. RESULTS: We identified 16 eyes of 11 patients with MC on fundus examination. Based on OCT imaging features, conforming variant of MC was seen in 9 (56%) eyes and non-conforming variant in 7 (44%) eyes. No eyes with MC in the study showed features of both conforming and non-conforming varieties simultaneously. In the non-conforming variety of MC with presence of intercalary membrane break, ICC was identified in 5 (71%) of these eyes. ICC in MC appeared as flat, dark greenish areas with or without an orange-coloured boundary abutting the margin of the coloboma on Multicolour® imaging. CONCLUSION: In 31% eyes, ICC was seen in non-conforming type of MC and was well-identified on Multicolour® imaging. It appears that presence of intercalary membrane break and detachment are prerequisites for developing ICC.

A Systematic Review of the Clinical Manifestations and Diagnostic Methods for Macular Coloboma.

Objectives: To present the clinical features of and diagnostic methods used for macular coloboma (MC), and to analyze the factors associated with best-corrected visual acuity (BCVA) in patients with MC.Methods: A systematic review using the MEDLINE (PubMed), EMBASE, LILACS, and Cochrane databases was performed. The factors associated with BCVA were analyzed.Results: A total of 21 patients (mean age at diagnosis, 18.1 ± 14.6 years) with 36 eyes affected by MC (5 unilateral, 16 bilateral) were included in the study. All 21 patients (100%) had undergone a good-quality fundus examination. The size of the MC lesions ranged from 1.0 × 1.2 to 4.0 × 4.0 disc diameters (DD). Twenty-seven (73%) eyes had pigmented MC, seven (19%) had non-pigmented MC, and one (3%) had an unspecific type. The diagnosis was confirmed using spectral-domain optical coherence tomography (SD-OCT) in 16 (43.2%) eyes. A positive correlation was found between BCVA and the type of MC (ß = 0.876, p = .006) and abnormal eye movement (ß = 0.087, p = .018), and a negative correlation was found between BCVA and a contributory medical history of ventricular septal defect (ß = -0.327, p = .001).Conclusions: Pigmented MC was the most common type and had the highest possibility of causing impaired vision in the affected eyes. Additionally, joint examinations should be applied for diagnostic confirmation of MC. Furthermore, fundoscopy, electroretinogram, electrooculography, fundus fluorescein angiography, and SD-OCT are all critical for differential diagnosis of MC-like lesions.

Coffin-Siris syndrome with bilateral macular dysplasia caused by a novel exonic deletion in ARID1B.

Coffin-Siris syndrome (CSS) is a congenital anomaly syndrome characterized by developmental delay, coarse facial features, and hypoplasia of the fifth digit's nail or phalanges. Herein, we report a case of the 8-year-old female patient who showed developmental delay associated with dysplasia in the macular and large toe area. Comprehensive genomic analysis showed no possible candidate variants, but the subsequent genomic copy number analysis revealed a novel exonic deletion in the coding region of AT-rich interactive domain-containing protein 1B (ARID1B), a gene responsible for CSS. Genomic copy number analysis can aid in diagnosing CSS by confirming undiagnosed exonic deletions in ARID1B. Furthermore, this is the first report of CSS associated with bilateral macular dysplasia.

Dome-shaped macula in children and adolescents.

PURPOSE: We sought to evaluate the incidence and characteristics of dome-shaped macula (DSM) in children and adolescents with myopia. METHODS: A retrospective review of medical records was performed to identify subjects who were younger than 19 years with myopia of -3.0 diopters or greater. The results of optical coherence tomography images were analyzed to identify DSM. The height and diameter of the dome were measured. Age, best-corrected visual acuity (BCVA), and refractive error of study participants who exhibited DSM were compared with those of patients who did not. RESULTS: Among the 1,042 eyes of 615 patients, eight eyes (0.77%) of seven patients had DSM. Six of these eight eyes were not highly myopic (i.e., less than -6.0 diopters of spherical equivalents). Additionally, the mean height and diameter of the identified domes were 146.50 ± 42.33 µm and 4779.75 ± 699.38 µm, respectively. Patients with DSM were significantly older (mean age: 15.88 ± 2.36 years) than patients without it (11.51 ± 4.60 years; p = 0.007). The youngest affected patient was 11 years old. There was no significant difference in refractive errors (p = 0.629) or BCVA (p = 0.314) between the two groups. CONCLUSIONS: Although the incidence in this study was very low, DSM was found even in children and adolescents. In addition, 75% of affected individuals were not highly myopic. These results suggest that inherent traits may be involved in development of DSM.

Resolution of Unilateral Dome-Shaped Macula With Serous Detachment After Treatment of Topical Carbonic Anhydrase Inhibitors.

Dome-shaped macula (DSM) is a morphological feature outlined through the use of optical coherence tomography and characterized by an inward or anterior deviation of the macula with respect to chorioretinal concavity. Currently, there is no validated therapy for serous retinal detachment secondary to DSM. The authors report a case of childhood unilateral DSM in a hyperopic eye with normal axial length that was complicated with subretinal fluid (SRF). Topical carbonic anhydrase inhibitors may be an acceptable and safer option for patients presented with nonresolving SRF associated with DSM. Further randomized controlled trials are necessary to confirm the efficacy of this therapeutic approach. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e218-e221.].

Alport syndrome with bilateral simultaneous anterior and posterior lenticonus with severe temporal macular thinning.

Alport syndrome (AS) is a hereditary disease with various modes of inheritance, X-linked being the the most common. Anterior lenticonus is the characteristic abnormality along with perimacular and peripheral fleck retinopathy. Our two cases of AS had simultaneous anterior and posterior lenticonus with severe temporal macular thinning on optical coherence tomography with no specific renal symptomatology and were diagnosed as AS without any invasive renal biopsy. First patient was a 19-year-old man who presented with compound myopia due to bilateral anterior and posterior lenticonus with perimacular fleck retinopathy and lozenge sign and bilateral moderate sensorineural hearing loss (SNHL). Second patient was a 24-year-old man who presented with difficulty in vision due to bilateral anterior and posterior lenticonus with bilateral severe SNHL. Our cases emphasise the crucial role of an ophthalmologist in diagnosing AS before the onset of renal symptoms and prompting further nephrological work-up in the patient or the carrier.

Bilateral congenital macular coloboma and cataract: A case report.

RATIONALE: The case with congenital macular coloboma and cataract was rarely reported, and the pathogenic gene of the disease is still not clear. Moreover, it is difficult to improve the visual acuity of the eye with this disease. PATIENT CONCERNS: An 11-year-old boy presented low visual acuity and horizontal nystagmus in both eyes. Ophthalmologic examination showed the patient with bilateral congenital coloboma and cataract. The visual acuity of the patient improved slightly after cataract surgery. Heterozygous mutations of frizzled-4 (FZD4) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) were identified by next-generation sequencing in this case. DIAGNOSIS: Congenital macular coloboma and cataract of both eyes. INTERVENTIONS: We performed the standard phacoemulsification and intraocular lens implantation on both eyes of the patient for the treatment of congenital cataract, and then followed up the fundus lesions regularly. OUTCOMES: Cataract surgery may improve the visual acuity of the eyes with congenital macular coloboma and cataract at some degree, but the vision of this patient was still very poor postoperatively. Furthermore, the heterozygous mutations of FZD4 and NOD2 were found in this patient. LESSONS: Cataract surgery may improve the visual acuity of the eyes with congenital macular coloboma and cataract at some degree, and heterozygous mutations of FZD4 and NOD2 may be involved in the occurrence of congenital macular coloboma and cataract.

Macular maldevelopment in ATF6-mediated retinal dysfunction.

Background: Achromatopsia has been previously associated with mutations in the ATF6 gene. Rod-monochromatism, foveal hypoplasia, and disruption of the subfoveal photoreceptor layer are described as phenotypical features. We report detailed structural and electrophysiological assessment of two patients from two families, one manifesting severe macular maldevelopment and one with foveal hypoplasia.Materials and methods: The patients underwent a complete ophthalmic examination including electroretinography (ERG), spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence, and fundus photography. Genetic testing was performed by next-generation sequencing.Results: In one patient, fundoscopy and SD-OCT revealed well-demarcated coloboma-like excavated lesions at the central macula of both eyes. Genetic analysis identified a novel homozygous p.Asp140Ter mutation in the ATF6 gene. The second patient had foveal hypoplasia in association with a homozygous ATF6 mutation affecting a splice donor site (c.1187 + 5G>C). In both patients, electrophysiological assessment showed normal rod-specific (DA 0.01) and dark-adapted bright white-flash ERGs (DA 10.0). 30 Hz flicker ERGs were undetectable. There were low-amplitude single-flash photopic ERGs (LA 3.0) with timing and shape suggesting S-cone origin.Conclusions: The findings, particularly a case with severe macular maldevelopment, may expand on the phenotype previously associated with ATF6-mediated achromatopsia. In addition, the comprehensive electrophysiological assessment suggests that preserved S-cone activity can be detected in this particular molecular sub-type of cone dysfunction.

FACTORS ASSOCIATED WITH SEROUS RETINAL DETACHMENT IN HIGHLY MYOPIC EYES WITH VERTICAL OVAL-SHAPED DOME.

PURPOSE: This study investigated factors associated with persistent serous retinal detachment in highly myopic eyes with vertical oval-shaped domes. METHODS: Twenty-eight highly myopic patients (40 eyes) with smooth macular elevations related to a vertical oval-shaped dome were recruited. Serous retinal detachment was investigated; 11 eyes had persistent submacular fluid (study group) and 29 eyes lacked submacular fluid (control group). All patients underwent complete ophthalmologic examinations, including axial-length measurement and fluorescein angiography. Spectral domain optical coherence tomography scans through the fovea measured choroidal thicknesses, macular bulge height, and vitreoretinal interface factors. RESULTS: No studied variables (age, sex, spherical equivalence, axial length, vitreomacular traction, epiretinal membrane, and internal limiting membrane detachment) except higher macular bulge height (P = 0.03) and a reduced macular choroidal thickness (P = 0.02) were associated with the risk of serous retinal detachment. No statistically significant differences in best-corrected visual acuity were observed between the study and control groups. Serous retinal detachment always occurred at the top of the inward incurvation of the macula and was characterized by multiple hyperfluorescent granular patches on fluorescein angiography. CONCLUSION: A higher macular bulge height and a reduced macular choroidal thickness might be important factors in the development of serous retinal detachment in patients with vertical oval-shaped domes.

Spectrum of choroidal neovascularisation associated with dome-shaped macula.

AIMS: To investigate the clinical spectrum of choroidal neovascularisation (CNV) in patients with dome-shaped macula with the aid of multimodal imaging. METHODS: In this cross-sectional, retrospective, observational study, we reviewed charts and imaging studies of 144 eyes of 79 consecutive patients with dome-shaped macula evaluated at a tertiary referral centre, including optical coherence tomography angiography (OCTA), fluorescein angiography (FA) and indocyanine green angiography (ICGA). Three masked graders evaluated the prevalence and type of CNV. Primary outcome measures were the diagnostic agreement between OCTA and FA±ICGA, the multimodal imaging characteristics and prevalence of CNV associated with dome-shaped macula. RESULTS: We identified 30 eyes with dome-shaped macula complicated by CNV with an estimated prevalence of 20.8% (95% CI 14.2 to 27.4). Twenty-two eyes (73%) showed a type 2 CNV while eight eyes (27%) showed a type 1 CNV. Serous macular detachment was present in 39 eyes (27%) and harboured a CNV in five cases (13%). The overall diagnostic agreement between OCTA and FA±ICGA was excellent (k=0.894, p<0.001), but only the use of both techniques allowed the identification of the whole pool of CNVs. CONCLUSION: Eyes with dome-shaped macula may either develop typical myopic CNV (ie, type 2 CNV) or pachychoroid-associated CNV (ie, type 1 CNV), similar to those observed in central serous chorioretinopathy. Accordingly, in case of serous macular detachment complicating dome-shaped macula, the presence of an associated CNV should be considered. When suspecting a CNV associated with dome-shaped macula, the application of both OCTA and FA±ICGA is superior to the use of one technique alone.

Observational study of clinical characteristics of dome-shaped macula in Chinese Han with high myopia at Zhongshan Ophthalmic Centre.

PURPOSE: To evaluate the prevalence of dome-shaped macula (DSM) in highly myopic eyes among Chinese Han and to detect the correlation with myopic maculopathy and macular complications. METHODS: A total of 736 Chinese Han patients (1384 eyes) with high myopia (refractive error≤6.0 diopters or axial length ≥26.5 mm) are reviewed based on information entered into a high-myopia database at Zhongshan Ophthalmic Centre. Subfoveal choroidal thickness (SFCT) and parafoveal choroidal thickness (PFCT) are measured. The prevalence of DSM in patients with myopic maculopathy is categorised from C0 to C4. Clinical features, including macular complications, SFCT and PFCT, are compared between myopic eyes with and without DSM. RESULTS: Among the 1384 eyes, 149 (10.77%) show DSM. In highly myopic eyes without macular complications, the best corrected visual acuity is significantly worse in patients with DSM (p=0.002), and the ratio between subfoveal and parafoveal choroidal thickness (S/PCT) is significantly elevated in patients with DSM (p=0.021). The proportion of foveal schisis (17.24% vs 62.86%) is much lower in eyes with DSM compared with those without DSM. However, the proportions of extrafoveal schisis (39.66% vs 5.37%), foveal serous retinal detachment (SRD) (5.17% vs 0) and epiretinal membrane (ERM) (24.14% vs 10.74%) are much higher in eyes with DSM. The proportion of DSM was lower in C0 and C1, but higher proportion of DSM was found in C3 and C4. CONCLUSIONS: DSM is found in 10.77% of highly myopic eyes among Chinese Han. DSM might be a protective mechanism for foveal schisis and a risk factor for extrafoveal schisis, SRD and ERM.

Choroidal Neovascularization in Torpedo Maculopathy Assessed on Optical Coherence Tomography Angiography.

Torpedo maculopathy is characterized by a congenital, unilateral, and torpedo-shaped chorioretinal lesion with unclear pathogenesis and evolution. Although the optical coherence tomography angiography (OCTA) characteristics have already been defined in literature, the authors describe for the first time the presence of choroidal neovascularization (CNV) on the temporal edge of this lesion in a 36-year-old woman with a history of altered visual field in her left eye. The authors' investigation supports the hypothesis of an aberrant choroidal circulation underlying the pathogenesis of this condition, and proves the advantage conferred by OCTA in CNV detection over the other angiographic techniques. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:e210-e213.].

Bilateral congenital macular coloboma: Swept-source optical coherence tomography findings.

A 15-year-old male presented with decreased vision and nystagmus from childhood. Best-corrected visual acuity was limited to 0,05/10 in both eyes. Fundus examination revealed a well-demarcated macular excavation of 2 discs diameter, baring of the underlying sclera, surrounded by a pigmented rim and hypopigmented retinal areas. Autofluorescence images showed a central hypoautofluorescent lesion with patchy hypoautofluorescent areas corresponding to retinal pigmented epithelium (RPE) and photoreceptor atrophy. Swept-source optical coherence tomography showed a crater-like depression with atrophy of the neurosensory retina and the absence of RPE and choroid except some large choroidal vessels. Anti-toxoplasma antibody was negative. These findings are suggestive of a congenital macular coloboma. Similar lesions have to be excluded such as toxoplasmosis macular scar and North Carolina dystrophy.