Congenital Microphthalmia Research Articles

Microphthalmia and disrupted retinal development due to a LacZ knock-in/knock-out allele at the Vsx2 locus.

Visual System Homeobox 2 (Vsx2) is a transcription factor expressed in the developing retina that regulates tissue identity, growth, and fate determination. Several mutations in the Vsx2 gene exist in mice, including a spontaneous nonsense mutation and two targeted missense mutations originally identified in humans. Here, we expand the genetic repertoire to include a LacZ reporter allele (Vsx2 LacZ ) designed to express beta-Galactosidase (b-GAL) and simultaneously disrupt Vsx2 function (knock-in/knock-out). The retinal expression pattern of b-GAL is concordant with VSX2, and the mutant allele is recessive. Vsx2 LacZ homozygous mice have congenital bilateral microphthalmia accompanied by defects in retinal development including ectopic expression of non-retinal genes, reduced proliferation, delayed neurogenesis, aberrant tissue morphology, and an absence of bipolar interneurons - all hallmarks of Vsx2 loss-of-function. Unexpectedly, the mutant VSX2 protein is stably expressed, and there are subtle differences in eye size and early retinal neurogenesis when compared to the null mutant, ocular retardation J. The perdurance of the mutant VSX2 protein combined with subtle deviations from the null phenotype leaves open the possibility that Vsx2 LacZ allele is not a complete knock-out. The Vsx2 LacZ allele exhibits loss-of-function characteristics and adds to the genetic toolkit for understanding Vsx2 function.

Determining Asymmetry Thresholds in Anophthalmia/Microphthalmia Using a Three-dimensional Animated Model.

Congenital microphthalmia and anophthalmia are rare development disorders with underdevelopment of the orbital region, resulting in asymmetry of the face. No clear guidelines exist to determine when these deviations are acceptable. The face of a healthy 6-year-old child was three-dimensionally scanned. On this scan, we modeled various incremental degrees of facial asymmetries using three-dimensional modeling software. We modeled for smaller palpebral fissures, sunken eyes, and downward displacement of the eye. We also tested whether adjusting the vertical palpebral fissure height in relation to the horizontal palpebral fissure width affected perception. A total of 22 videos were created in which the model turned the head horizontally and vertically. We created a questionnaire asking raters how acceptable the face is, on a linear scale from 0 to 10. Results showed a correlation between the degree of asymmetry and the acceptability score of the raters. Enophthalmos of ≥6 mm, palpebral fissure width ≤79% compared with the other eye, and 2 mm or more downward displacement of the eye resulted in a significant different acceptability score. The desire for correction was strongly increased when these thresholds were exceeded. Adjusting the vertical palpebral fissure height to the horizontal palpebral fissure width resulted in a worse acceptability score. A unilateral sunken eye (enophthalmos) of 6 mm or more, asymmetric horizontal palpebral fissure length of ≤79%, and a lower position of one eye of more than 2 mm resulted in unacceptable judgment. These data can be used to evaluate treatment outcome in children treated for congenital microphthalmia and anophthalmia.

A naturally occurring canine model of syndromic congenital microphthalmia.

In humans, the prevalence of congenital microphthalmia is estimated to be 0.2-3.0 for every 10,000 individuals, with nonocular involvement reported in ∼80% of cases. Inherited eye diseases have been widely and descriptively characterized in dogs, and canine models of ocular diseases have played an essential role in unraveling the pathophysiology and development of new therapies. A naturally occurring canine model of a syndromic disorder characterized by microphthalmia was discovered in the Portuguese water dog. As nonocular findings included tooth enamel malformations, stunted growth, anemia, and thrombocytopenia, we hence termed this disorder Canine Congenital Microphthalmos with Hematopoietic Defects. Genome-wide association study and homozygosity mapping detected a 2 Mb candidate region on canine chromosome 4. Whole-genome sequencing and mapping against the Canfam4 reference revealed a Short interspersed element insertion in exon 2 of the DNAJC1 gene (g.74,274,883ins[T70]TGCTGCTTGGATT). Subsequent real-time PCR-based mass genotyping of a larger Portuguese water dog population found that the homozygous mutant genotype was perfectly associated with the Canine Congenital Microphthalmos with Hematopoietic Defects phenotype. Biallelic variants in DNAJC21 are mostly found to be associated with bone marrow failure syndrome type 3, with a phenotype that has a certain degree of overlap with Fanconi anemia, dyskeratosis congenita, Shwachman-Diamond syndrome, Diamond-Blackfan anemia, and reports of individuals showing thrombocytopenia, microdontia, and microphthalmia. We, therefore, propose Canine Congenital Microphthalmos with Hematopoietic Defects as a naturally occurring model for DNAJC21-associated syndromes.

Dysregulation of Autophagy Occurs During Congenital Cataract Development in βA3ΔG91 Mice.

To examine lens phenotypic characteristics in βA3ΔG91 mice and determine if βA3ΔG91 affects autophagy in the lens. We generated a βA3ΔG91 mouse model using CRISPR/Cas9 methodology. Comparative phenotypic and biochemical characterizations of lenses from postnatal day 0 (P0), P15, and 1-month-old βA3ΔG91 and wild-type (WT) mice were performed. The methodologies used included non-invasive slit-lamp examination, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blot, and immunohistochemical (IHC) analyses to determine the levels of autophagy-related genes and proteins. Transmission electron microscopy (TEM) analysis of lenses was performed to assess organelle degradation and the presence of autophagic vesicles. TUNEL staining was used to determine apoptosis in the lens. Relative to WT lenses, 1-month-old βA3ΔG91 mice developed congenital nuclear cataract and microphthalmia and showed an early loss of endoplasmic reticulum (ER) in the cortex and attenuation of nuclei degradation. This observation was confirmed by TEM analysis, as was the presence of autophagic vesicles in βA3ΔG91 lenses. Comparative IHC and RT-qPCR analyses showed relatively higher levels of autophagy markers (ubiquitinated proteins and p62, LC3, and LAMP2 proteins) in βA3ΔG91 lenses compared to WT lenses. Additionally, βA3ΔG91 lenses showed relatively greater numbers of apoptotic cells and higher levels of cleaved caspase-3 and caspase-9. The deletion of G91 in βA3ΔG91 mice leads to higher levels of expression of autophagy-related proteins and their transcripts relative to WT lenses. Taken together, G91 deletion in βA3/A1-crystallin is associated with autophagy disruption, attenuation of nuclei degradation, and cellular apoptosis in the lens, which might be congenital cataract causative factors.

Long term follow-up of axial length and orbital dimensions in congenital microphthalmia and anophthalmia.

To evaluate axial length (AL), orbital width (OW) and height (OH) development in congenital microphthalmia and anophthalmia (MICA) using serial ultrasonography measurements. A longitudinal prospective cohort (n = 74) of unilaterally and bilaterally affected MICA patients was followed from 2013 to 2022 at the university hospital in Amsterdam, the Netherlands. Clinical entity, age, severity category based on axial length, conformer treatment and intra-orbital cysts were registered. The main outcome measures were the absolute and relative growth of AL, OW and OH. Surgical and intra-orbital cyst cases were described separately. Absolute microphthalmic eye size increased in 27/49 (55%) unilateral MICA eyes, but growth arrest/decrease in the remaining could shift the case to a more severe category over time. A final affected/unaffected orbital symmetry ≥80% was seen in the large majority of unilateral cases (45/46 for OW, 43/46 for OH). Cases with AL < 10.5 mm had orbital symmetry <80% more often. Most orbital symmetry changes were seen in moderate and severe unilateral cases treated with 3D-printed conformer therapy starting at age <1 year, with 6/10 (60%) symmetry increase, 30% unchanged symmetry and 10% symmetry decrease. All cases older than 6.5 years (n = 6) did not show any change anymore, regardless of treatment. For bilateral and unilateral mild cases, orbital dimensions kept the same proportions during follow-up, with or without conformer treatment. Using severity categories in MICA based on relative AL may aid the decision to start conformer treatment, as most orbital symmetry changes were seen in moderate and severe unilateral cases receiving 3D-printed conformer therapy that started under age 1.

Microphthalmia with a Large Orbital Cyst: A Case Report

Purpose: We present the case of a 4-month-old boy with a large orbital cyst that caused lateral displacement of the optic nerve resulting in progressive exophthalmos of the left eye since birth.Case summary: A 4-month-old boy presented with progressive exophthalmos of the left eye since birth. Physical examination revealed marked left eye proptosis. Magnetic resonance imaging revealed microphthalmia and a 2.2 × 1.9 cm orbital cyst in the retrobulbar region. Subsequently, an anterior orbitotomy of the left eye was performed to dissect and excise the cyst. Histopathological examination revealed an orbital cyst containing neuroectodermal tissue. No complications or recurrences were observed during the 3-month post-surgery period.Conclusions: Congenital microphthalmia with orbital cysts is a rare condition that does not always require surgical intervention. However, timely surgical intervention in cases of severe exophthalmos can result in favorable functional and cosmetic outcomes. We present a case that exhibited significant improvement following surgical removal of the orbital cyst.

Stepwise self-inflating hydrogel expansion for congenital anophthalmia and blind microphthalmia: Over 15 years’ experience in China

BackgroundSelf-inflating hydrogel expanders have been used to treat anophthalmia and blind microphthalmia. This study aimed to investigate the long-term outcomes of treatment with self-inflating hydrogel expanders for congenital anophthalmia and blind microphthalmia. MethodsIn this retrospective study, the medical records of 161 patients with anophthalmia and blind microphthalmia who underwent hydrogel expansion were reviewed. We measured the palpebral fissure height (PFH), palpebral fissure length (PFL), and distance between the inner canthal and mid-nasal line (ICMN) before and after surgery. Cox regression analysis was conducted to determine which variables were related to the implantation of spherical expanders following hemispherical expander implantation. ResultsAfter treatment, the PFH and PFL increased significantly (p < 0.001). Complications including expander migration and extrusion occurred in 15 cases. Five patients needed enucleation or further dermis fat graft implantation because of insufficient expansion. The necessity for further spherical expansion was substantially related to a relative axial length (rAL) <0.5 (p = 0.007). ConclusionSelf-inflating hydrogel expansion can significantly increase the lid fissure. The occurrence of complications is rare, and surgical intervention can effectively address them. Abnormal eyes with a rAL of less than 0.5 demonstrate a higher possibility of needing additional orbital expansion.

A novel STAG1 variant associated with congenital clubfoot and microphthalmia: A case report

The cohesin protein complex plays a vital role in various cellular processes such as sister chromatid cohesion, chromosome condensation, DNA repair, and transcriptional regulation. It is constituted by SMC1, SMC3, RAD21, STAG1/STAG2 subunits, and several regulatory proteins. Pathogenic variants in these components cause cohesinopathies, with common clinical features including facial dysmorphism, delayed growth, developmental delay, and limb anomalies. Pathogenic variants in the STAG1 contribute to an emerging syndromic developmental disorder with only 21 reported cases in the literature. We describe a 3-year-old girl presenting with congenital bilateral clubfoot and unilateral microphthalmia—clinical manifestations not previously reported in the literature. Whole exome sequencing revealed a novel de novo nonsense variant (c.1183C&gt;T, p.(Arg395*)) in the STAG1, expanding the clinical and molecular spectrum of STAG1-related cohesinopathy. This patient’s unique phenotype highlights the clinical diversity within cohesinopathies, emphasizing their relevance in cases of developmental delay and dysmorphic features. Further studies, including genotype–phenotype correlation analyses and functional investigations, are essential for enhancing our understanding of STAG1-related cohesinopathy.

Identification of novel homozygous variants in FOXE3 and AP4M1 underlying congenital syndromic anophthalmia and microphthalmia.

Anophthalmia and microphthalmia are severe developmental ocular disorders that affect the size of the ocular globe and can be unilateral or bilateral. The disease is found in syndromic as well as non-syndromic forms. It is genetically caused by chromosomal aberrations, copy number variations and single gene mutations, along with non-genetic factors such as viral infections, deficiency of vitamin A and an exposure to alcohol or drugs during pregnancy. To date, more than 30 genes having different modes of inheritance patterns are identified as causing anophthalmia and microphthalmia. In the present study, a clinical and genetic analysis was performed of six patients with anophthalmia and microphthalmia and/or additional phenotypes of intellectual disability, developmental delay and cerebral palsy from a large consanguineous Pakistani family. Whole exome sequencing followed by data analysis for variants prioritization and validation through Sanger sequencing was performed to identify the disease causing variant(s). American College of Medical Genetics and Genomics (ACMG) guidelines were applied to classify clinical interpretation of the prioritized variants. Clinical investigations revealed that the affected individuals are afflicted with anophthalmia. Three of the patients showed additional phenotype of intellectual disability, developmental delays and other neurological symptoms. Whole exome sequencing of the DNA samples of the affected members in the family identified a novel homozygous stop gain mutation (NM_012186: c.106G>T: p.Glu36*) in Forkhead Box E3 (FOXE3) gene shared by all affected individuals. Moreover, patients segregating additional phenotypes of spastic paraplegia, intellectual disability, hearing loss and microcephaly showed an additional homozygous sequence variant (NM_004722: c.953G>A: p.Arg318Gln) in AP4M1. Sanger sequencing validated the correct segregation of the identified variants in the affected family. ACMG guidelines predicted the variants to be pathogenic. We have investigated first case of syndromic anophthalmia caused by variants in the FOXE3 and AP4M1. The present findings are helpful for understanding pathological role of the mutations of the genes in syndromic forms of anophthalmia. Furthermore, the study signifies searching for the identification of second variant in families with patients exhibiting variable phenotypes. In addition, the findings will help clinical geneticists, genetic counselors and the affected family with respect to prenatal testing, family planning and genetic counseling.

Clinical Characterization of Congenital Anophthalmic and Microphthalmic Cavities in Inidviduals With Craniofacial Anomalies.

Measure the frequency of anophthalmic and microphthalmic patients with craniofacial anomalies (FCAs). Descriptive, cross-sectional, retrospective study. Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo (HRAC-USP). The medical records of patients treated at HRAC from 2000 to 2012 with a diagnosis of congenital anophthalmia or microphthalmia were examined. Patients were excluded for secondary anophthalmia, incomplete medical records, or information that could not be accessed. Frequency of anophthalmia and microphthalmia; the proportions and diagnoses of associated FCAs; impairment of ocular appendages; extracranial or facial anomalies; genetic alterations; and surgical approach. A total of 56 patients had anophthalmia (52.3%), 35 had microphthalmia (32.7%), and 16 patients had both (15%). Individuals with FCAs associated with microphthalmia, anophthalmia, or both totaled 74, corresponding to 69.2%. Anophthalmia was more likely than microphthalmia to be accompanied by FCAs, at 76.4% of patients ( P < 0.05). Cleft lip and palate were the main malformations associated with anophthalmia (23.64%), with microphthalmia (45%), and with both (44.44%). Reconstructive surgery was done in 63.6% of cases. The ocular attachments were compromised in 71% of cases. Extracraniofacial malformations were found in 9.3% of patients. Only 7 records contained karyotypes, and no changes directly related to anophthalmia or microphthalmia were found. Anophthalmia is more frequent than microphthalmia and is more often accompanied by FCA. Cleft lip and cleft palate are the most frequent concomitant malformations.

Correlation Between the Computed Tomography and 3D Scanning System-Based Periorbital Morphology of Children with Congenital Microphthalmia

ABSTRACT Purpose This article aimed to explore the correlation between the periorbital morphology determined using a 3D scanning system and CT in congenital microphthalmia. Methods Fifty-two children with microphthalmia aged 0–6 were enrolled in this study. All the participants were subjected to orbital CT scans and 3D scanning. The CT and 3D scanning images were separately processed to obtain the orbital and facial parameters. Multivariate regression was used to analyze the correlation between 3D parameters and orbital volume. Results The orbital volume of the affected side (15.25 ± 3.35 cm3) was generally smaller than the unaffected side (18.58 ± 2.65 cm3, p < .001). Based on CT, at all ages, the parameters of the unaffected orbit were greater than the affected side. In the 3D scanning and 3D reconstruction based on CT, both unaffected and affected sides were highly correlated. A multiple linear regression equation including three 3D scanning factors was obtained for the orbital volume (R2 = 0.808, p < .001). Conclusions The retarded orbital volume could be estimated by the parameters based on 3D scanning, along with axial length. In the follow-up stage, 3D scanning can be a novel alternative method to assess the degree of orbital growth retardation in congenital microphthalmia.

Congenital Cataract and Narrow CSP: A Clue to Prenatal Diagnosis of RAB3GAP1-Associated Warburg Micro Syndrome

AbstractWarburg Micro Syndrome (WMS) is an autosomal recessive disorder characterized by intellectual disability, bilateral congenital cataracts, microphthalmia, and brain anomalies. We report an 18-week fetus presenting with bilateral congenital cataract and narrow cavum septum pellucidum. Patient was counselled about the possible etiologies ranging from infectious to chromosomal and single gene etiologies. Invasive testing for genetic analysis was done to determine etiology and establish prognosis. A previously reported homozygous frameshift mutation was identified in RAB3GAP1 gene leading to diagnosis of WMS. This case highlights the role of detailed fetal sonography and genetic testing to prognosticate pregnancies. Also WMS should be suspected in fetuses presenting with bilateral congenital cataract with or without brain anomalies.

Difference of anterior and posterior orbital development in patients with congenital microphthalmia: a retrospective cohort study from China

To evaluate volume differences between anterior and posterior orbit and demographic characteristics of Chinese patients with congenital microphthalmia. A retrospective cohort study, involving 169 unilateral congenital microphthalmia patients aged between 1 and 57 years old was conducted. Three-dimensional images of the orbit were generated from past CT scans, and digital orbital volume comprehensive measurement was done. The measured data included orbital volume (OBV), posterior orbital volume (POV), orbital width (OBW), orbital height (OBH), orbital depth (OBD), and posterior orbital area ratio. Significant differences were observed among OBV, POV, OBW, OBH, and OBD of the affected and unaffected eyes in different age-based groups (all P<0.001). Among them, OBH had the greatest different. The mean microphthalmic to contralateral ratio (MCR) of OBV, POV, OBW, and OBH continuously increased from 1 to 3 years old, whereas the MCR of POV decreased from 3 to 17 years old. The MCR of OBD was not found to be correlated to age. There was no significant difference between OBV, POV, OBW, and OBH in ages from 13 years old to adulthood (all P>0.05). The difference in posterior orbital area ratio between the affected and unaffected groups was not statistically significant (P>0.05). OBH is maximally affected, whereas OBD is minimally affected by microphthalmia. Posterior orbital retardation began 2y prior to orbital retardation and occurred at 3 years old in the affected eye, suggesting that intervention therapy should be done before the age of 4.

Design and Outcomes of a Novel Multidisciplinary Ophthalmic Genetics Clinic.

The Multidisciplinary Ophthalmic Genetics Clinic (MOGC) at the University of Michigan Kellogg Eye Center aims to provide medical and ophthalmic genetics care to patients with inherited ocular conditions. We have developed a clinical and referral workflow where each patient undergoes coordinated evaluation by our multidisciplinary team followed by discussions on diagnosis, prognosis, and genetic testing. Testing approaches are specific to each patient and can be targeted (single-gene, gene panel), broad (chromosomal microarray, whole-exome sequencing), or a combination. We hypothesize that this clinic model improves patient outcomes and quality of care. A retrospective chart review of patients in the MOGC from July 2020 to October 2022 revealed that the most common referral diagnoses were congenital cataracts, optic neuropathy, and microphthalmia, with 52% syndromic cases. Within this patient cohort, we saw a 76% uptake for genetic testing, among which 33% received a diagnostic test result. Our results support a tailored approach to genetic testing for specific conditions. Through case examples, we highlight the power and impact of our clinic. By integrating ophthalmic care with medical genetics and counseling, the MOGC has not only helped solve individual patient diagnostic challenges but has aided the greater population in novel genetic discoveries and research towards targeted therapeutics.

Outcomes of surgical treatment of congenital cataract with microphthalmia in infancy

Objective: To examine the outcomes of surgical treatment for infants with congenital cataract and microphthalmia (CATM). Methods: It was a retrospective case series study. Data of 28 (55 eyes) CATM children who underwent cataract surgery at the Qingdao Eye Hospital of Shandong First Medical University and were followed up for more than 5 years between January 2010 and December 2014 under the age of 6 months. There were 15 male and 13 female children. The age at the time of surgery was (3.2±1.3) months, and the follow-up time was (8.2±1.7) years. The data included the basic information of the children, the ocular biological parameters before and after surgery and intraocular lens (IOL) implantation, and the occurrence of complications. Paired t-tests or Wilcoxon signed rank tests were used to compare groups, and logistic regression analysis was used to identify factors related to IOL implantation, secondary glaucoma, and visual axis opacification (VAO). Results: The mean preoperative axial length was (16.6±1.0) mm, and the mean horizontal corneal diameter was (9.5±0.9) mm. The axial growth rate within 2 years after the first stage of surgery was (1.4±0.8) mm/year. None of the children had an IOL implanted before the age of 2. Sixty percent of the eyes (33/55) received IOL implantation within 2 to 4 years after the first stage of surgery, while the remaining 40% (22/55) did not receive IOL implantation at the last follow-up. The axial growth rate was (0.9±0.7) mm/year within two years after the second stage of surgery. Postoperative secondary glaucoma occurred in 7 eyes (12.7%), and VAO occurred in 15 eyes (27.3%). IOL implantation was associated with preoperative axial length (OR=0.072, P<0.001) and age at the first stage of surgery (OR=7.270, P<0.001), but not with preoperative corneal diameter (P=0.735). The incidence of VAO was associated with preoperative corneal diameter (OR=4.124, P=0.011), but not with age at the first stage of surgery (P=0.489) or preoperative axial length (P=0.489). No factors related to the occurrence of secondary glaucoma were found. The best corrected visual acuity at the last follow-up after IOL implantation was (0.37±0.28) logMAR, which was better than that of children without IOL implantation (0.67±0.19) logMAR (U=49.50, P=0.003). Conclusions: Children with CATM can obtain the opportunity for IOL implantation through early surgery and ultimately achieve good visual outcomes. Properly selecting the timing for implanting IOL can keep the incidence of secondary glaucoma at an acceptable level.

Congenital ocular cyst with microphthalmia – A case report

Congenital microphthalmia with intraorbital cyst is rare. Colobomatous cyst stems from defect in closure of embryonic fissure at the time of invagination of optic vesicle, leading to protrusion of neuroectodermal lined cystic mass from the defect in the wall of microphthalmic eye. Clinical presentation usually comprises progressively enlarging orbital cyst with microphthalmia. Enlargement of orbital cyst is attributable to continuous secretions from its wall. Imaging assessment evaluates lesion and its internal characteristics, organ of origin, and associated anomalies. Differentials include microphthalmia with cystic teratoma and meningoencephalocele. Management strategy comprises removal of cystic lesion or aspiration, followed by sclerotherapy with bleomycin injection and ocular expander to maintain orbital volume for prosthesis.

Abnormalities of the contralateral eye in unilateral congenital anophthalmic or blind microphthalmic patients

To describe the prevalence, distribution, and features of anterior and posterior segment abnormalities in the contralateral eye in cases unilateral of anophthalmia and blind microphthalmia. The medical records of patients with unilateral congenital anophthalmia and blind microphthalmia referred to Beijing Tongren Hospital between January 2017 and December 2021 were reviewed retrospectively to investigate the prevalence of abnormalities of the fellow eye. A total of 168 patients were included. Of these, 28 (16.7%) had fellow eye abnormalities, 4 (2.4%) with anterior segment involvement in the contralateral eye. All 28 had fundus abnormalities. The most common posterior segment finding was coloboma (7.7%), followed by optic nerve dysplasia (3.0%), familial exudative vitreoretinopathy (FEVR) or FEVR-like fundus (1.8%), morning glory disk anomaly (1.8%), and retinal nerve fiber layer defect (1.2%). High myopia fundus changes (0.6%), retinal folds (0.6%), maculopathy (0.6%), peripapillary staphyloma (0.6%), and Bergmeister optic disk (0.6%) were also noted. Patients with unilateral congenital anophthalmia or blind microphthalmia have a high probability of contralateral eye disease. The most common abnormality is coloboma.

Non-vasogenic cystoid maculopathies.

Besides cystoid macular edema due to a blood-retinal barrier breakdown, another type of macular cystoid spaces referred to as non-vasogenic cystoid maculopathies (NVCM) may be detected on optical coherence tomography but not on fluorescein angiography. Various causes may disrupt retinal cell cohesion or impair retinal pigment epithelium (RPE) and Müller cell functions in the maintenance of retinal dehydration, resulting in cystoid spaces formation. Tractional causes include vitreomacular traction, epiretinal membranes and myopic foveoschisis. Surgical treatment does not always allow cystoid space resorption. In inherited retinal dystrophies, cystoid spaces may be part of the disease as in X-linked retinoschisis or enhanced S-cone syndrome, or occur occasionally as in bestrophinopathies, retinitis pigmentosa and allied diseases, congenital microphthalmia, choroideremia, gyrate atrophy and Bietti crystalline dystrophy. In macular telangiectasia type 2, cystoid spaces and cavitations do not depend on the fluid leakage from telangiectasia. Various causes affecting RPE function may result in NVCM such as chronic central serous chorioretinopathy and paraneoplastic syndromes. Non-exudative age macular degeneration may also be complicated by intraretinal cystoid spaces in the absence of fluorescein leakage. In these diseases, cystoid spaces occur in a context of retinal cell loss. Various causes of optic atrophy, including open-angle glaucoma, result in microcystoid spaces in the inner nuclear layer due to a retrograde transsynaptic degeneration. Lastly, drug toxicity may also induce cystoid maculopathy. Identifying NVCM on multimodal imaging, including fluorescein angiography if needed, allows guiding the diagnosis of the causative disease and choosing adequate treatment when available.

Socket expansion with conformers in congenital anophthalmia and microphthalmia

To report the outcomes of acrylic conformer-assisted socket expansion in congenital anophthalmia and microphthalmia. In this noncomparative, interventional case series, the medical records of 24 eyes of 18 consecutive patients with congenital anophthalmia (n = 3), clinical anophthalmia (n=8), and microphthalmia (n = 13) were reviewed retrospectively. Twelve cases were unilateral; 6 were cases bilateral (3 clinical anophthalmia and 3 microphthalmia). Serial socket expansion with progressively larger acrylic conformers was managed in clinic. Horizontal palpebral fissure (HPF) width was graded as good (final HPF ≥20 mm, or interocular difference ≤2 mm for unilateral cases), fair (17-19 mm, or 3 mm interocular difference), or poor (<17 mm, or ≥4 mm difference). The mean initial lid lengths in anophthalmia, clinical anophthalmia, and microphthalmia were 11.0, 12.4, and 16.9, increasing to 21.0, 19.9, and 22.2, respectively, over a mean period of 51 months. Mean age at the initiation of treatment was 19 months (range, 1-78). Percentage increases in lid length were 90.9%, 61.2%, and 31.3% in anophthalmia, clinical anophthalmia, and microphthalmia, respectively, with an average 7 conformer exchanges. For unilateral cases, the mean final lid length of involved eyes was 22.3 mm, comparable to 23.5 mm in normal contralateral eyes. Good outcomes were achieved in 18 orbits (75%); fair outcomes, in 6 (25%) cases. None of the sockets had poor expansion at final follow-up. All cases had good cosmesis with acceptable prosthesis wear at last visit. In our patient cohort, good socket expansion was achieved with acrylic conformers alone in congenital anophthalmia and microphthalmia, with acceptable prosthesis wear.

Intraorbital self-inflating hydrogel expander implantation with a modified technique in congenital microphthalmia

PurposeTo investigate the long-term outcomes of intraorbital self-inflating hydrogel expander implantation with optic nerve transection in children with congenital microphthalmia. MethodsThe medical records of unilaterally blind microphthalmic pediatric patients undergoing intraconal hydrogel expander implantation with optic nerve transection were reviewed retrospectively. For each patient, the microphthalmic eye was preserved. The orbital volume and globe volume were measured and analyzed based on computed tomography scans taken preoperatively and 36 months postoperatively. The palpebral length was measured between the medial and lateral canthus at every follow-up. Surgical complications were also recorded. ResultsTwelve patients were included (median age, 44.25 ± 17.5 months). At 36 months postoperatively, the microphthalmic and contralateral orbital volumes increased by 3.07 ± 0.77 ml and 2.03 ± 0.67 ml, respectively. The mean microphthalmic/contralateral ratio (MCR) of the orbital volume increased significantly from 76.60% ± 5.46% to 83.81% ± 5.41% (P < 0.001). The microphthalmic palpebral length increased by 6.17 ± 1.85 mm, whereas the contralateral palpebral length increased by 2.67 ± 1.44 mm. Significant changes were observed in the palpebral length MCR (68.00% ± 4.83% vs 85.07% ± 3.87%; P < 0.001). There was no significant change in the microphthalmic globe volume at 36 months postoperatively (P = 0.215). For the fellow eye, the globe volume increased significantly by 0.53 ± 0.34 ml (P < 0.001). During the follow-up period, 2 patients developed a sunken prosthesis. One patient had difficulty opening the eye after wearing the conformer. There were no cases of expander rejection or extrusion. ConclusionsIn this small cohort of patients with congenital microphthalmia, intraorbital self-expanding hydrogel expander implantation with optic nerve transection led to excellent osseous and eyelid growth throughout the 36-month follow-up period.