Posterior microphthalmos with achievement of good visual acuity and disappearance of papillomacular retinal folds: a case report.

BACKGROUND: Posterior microphthalmos (PM) is a rare condition with poor visual prognosis even after amblyopia treatment. We report a case of PM with achievement of good visual acuity and disappearance of papillomacular retinal folds (PFs) over a period of 7 years. CASE PRESENTATION: A girl aged 3 years and 5 months was referred to our hospital, after poor visual acuity was identified at a medical checkup for 3-year-olds. She had severe spherical hyperopia: + 17.25 D in the right eye (RE) and + 18 D in the left eye (LE). Her corrected visual acuity was 20/200 in the RE and 20/250 in the LE. PFs were observed in both eyes on optical coherence tomography (OCT), and the diagnosis of PM was made based on the normal corneal diameter and anterior chamber depth. During the course of the disease, a gradual decrease in the height of the PFs was observed on OCT. The corrected visual acuity at age 10 years was 20/20 in the RE and 20/25 in the LE. CONCLUSIONS: The visual prognosis of PM is poor, and only one case with good visual acuity has been reported in the literature. The patient in the present case not only developed good visual acuity, but also showed improvement in macular morphology, which was not noted in previous reports. Early diagnosis of PM and early amblyopia treatment is important for the visual development in PM.

Comparisons of size of foveal avascular zone area among children with posterior microphthalmos, high hyperopia, and normal eyes.

PURPOSE: To determine the area of the surface foveal avascular zone (FAZ) in children with posterior microphthalmos (PM), high hyperopia, and normal eyes using optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: Thirty-six children were studied including 6 cases 12 eyes of PM (mean age 9.5 ± 5.2 years), 15 cases 30 eyes of high hyperopia (6.9 ± 1.5 years), and 15 cases 30 eyes of healthy individuals (8.7 ± 1.7 years). The B- and C-scan images in all children were recorded by OCT and OCTA with a scanning area of 3.0 × 3.0 mm centered on the fovea. All images were corrected for axial length differences, and the area of the FAZ surface and central macular thickness (CMT) was measured manually and compared. RESULTS: The area of FAZ in the PM group was 0.007 ± 0.003 mm2, which was significantly smaller than that in the high hyperopia eyes at 0.286 ± 0.108 mm2 and healthy eyes at 0.318 ± 0.129 mm2 (both P < 0.001). The CMT in the PM group was 401.58 ± 33.60 mm, which was significantly thicker than in the high hyperopia eyes at 202.93 ± 12.28 mm and the normal eyes at 204.43 ± 18.76 mm. The area of the FAZ and CMT in the hyperopia group did not differ significantly from that of the normal healthy eyes. CONCLUSION: These findings indicate that patients with PM have a hypoplastic macular region, which must be considered in any treatment of these eyes.

Ocular Spiroplasma ixodetis in Newborns, France.

Cataract and uveitis are rare in newborns but potentially blinding. Three newborns with cataract and severe anterior uveitis underwent cataract surgery. Spiroplasma ixodetis was detected in lens aspirates using bacterial 16S-rRNA PCR and transmission electron microscopy. These findings, which suggest maternal-fetal infection, are consistent with previous experimental Spiroplasma-induced cataract and uveitis.

The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort.

Nanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We recruited 40 individuals from 13 kindreds with nanophthalmos or posterior microphthalmos, with 12 probands subjected to exome sequencing. Nine probands (69.2%) were assigned a genetic diagnosis, with variants in MYRF, TMEM98, MFRP, and PRSS56. Two of four PRSS56 families harbored the previously described c.1066dupC variant implicated in over half of all reported PRSS56 kindreds, with different surrounding haplotypes in each family suggesting a mutational hotspot. Individuals with a genetic diagnosis had shorter mean axial lengths and higher hyperopia than those without, with recessive forms associated with the most extreme phenotypes. These findings detail the genetic architecture of nanophthalmos and posterior microphthalmos in a cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.

Swept source-OCT and swept source-OCT angiography findings in posterior microphthalmos.

PURPOSE: To describe swept source-OCT (SS-OCT) and swept source-OCT angiography (SS-OCTA) findings in eyes with posterior microphthalmos (PM). METHODS: Twelve eyes (six patients) with PM were evaluated using SS-OCT and SS-OCTA. Structural changes, subfoveal choroidal thickness (SFCT), and perifoveal capillary changes with qualitative and quantitative assessments were analyzed. Twenty eyes served as control group. RESULTS: SS-OCT findings included elevated retinal papillo-macular fold (75%), retinal pigment epithelium folds (83%), macular cystoid spaces (42%), subretinal fluid (17%), and increased visibility of posterior vitreous cortex and hyaloid (42%). Mean SFCT in PM and in control eyes were 430.33 ± 157.48 µm and 290.05 ± 52.87 µm, respectively (p = 0.004). Perifoveal capillary changes on SS-OCTA included foveal avascular zone (FAZ) remodeling (100%), vessel tortuosity (67%), disorganization of the deep capillary network (67%), intraretinal cystoid spaces (42%), and areas of signal voids in the choriocapillaris (33%). FAZ area was significantly smaller in eyes with PM than in the control group in both the superficial (p < 0.001) and deep capillary plexuses (p = 0.001). Capillary vessel density (CVD) was significantly lower in the PM than in the control group in the deep capillary plexus (p = 0.004). Log MAR BCVA correlated negatively with axial length (r = - 0.929, p < 0.001), FAZ area in both the superficial (r = - 0.637, p < 0.001) and deep capillary plexus (r = - 0.561, p = 0002), and CVD in the deep capillary plexus (r = - 0.450, p = 0.016). CONCLUSIONS: Combined SS-OCT and SS-OCTA allow the detection of various retinal and choroidal structural and microvascular changes in eyes with PM. These findings can provide new insights onto this blinding ocular condition.

[Computed tomography imaging parameters of 82 Chinese patients with congenital microphthalmia].

Objective: To observe computed tomography (CT) imaging parameters of congenitally blind microphthalmia in Chinese patients and to provide clinical reference data for the Chinese population. Methods: It was a retrospective study for a consecutive case series of congenitally blind microphthalmia from July 2011 to July 2013. All of the patients were diagnosed in the Ocular Plastic Department, Tongren Eye Center, Beijing Tongren Hospital. We employed multi-section helical CT imaging with a computer-aided design system to observe and measure the imaging features in 82 Chinese patients (85 eyes). The paired T-test was applied for comparing the axial lengths, transverse diameters, and vertical diameters between the both sides in patients with congenital microphthalmia. The Pearson correlation was used for analyzing the relationship between the axial length and the age of the patients. Results: In the 82 patients, the age ranged from 1 month to 40 years old. Forty-one patients were male and 41 were female. The disease was unilateral in 96.34% of the patients. The orbital cysts were observed in 12.94% of them, and 76.47% of them presented basic structures on the CT scan. The abnormalities of the lens (62.35% of the eyes) and vitreous (82.35% of the eyes) were observed. The mean maximum axial length of the affected eyes (85 eyes) was (14.52±0.56) mm and the mean axial length of the unaffected eyes (79 eyes) was (22.79±0.36) mm. There was significantly statistical difference in the ocular size between the affected and unaffected eyes (t= 1.156, P<0.001) . Conclusions: Congenitally blind microphthalmia is usually complicated with the abnormalities of the lens and vitreous. The ocular size decreases significantly. The results of the present study provide a clinical reference for evaluating congenitally blind microphthalmia.(Chin J Ophthalmol, 2018, 54: 199-204).

Tietz/Waardenburg type 2A syndrome associated with posterior microphthalmos in two unrelated patients with novel MITF gene mutations.

Tietz syndrome and Waardenburg syndrome type 2A are allelic conditions caused by MITF mutations. Tietz syndrome is inherited in an autosomal dominant pattern and is characterized by congenital deafness and generalized skin, hair, and eye hypopigmentation, while Waardenburg syndrome type 2A typically includes variable degrees of sensorineural hearing loss and patches of de-pigmented skin, hair, and irides. In this paper, we report two unrelated families with MITF mutations. The first family showed an autosomal dominant pattern and variable expressivity. The second patient was isolated. MITF gene analysis in the first family demonstrated a c.648A>C heterozygous mutation in exon 8 c.648A>C; p. (R216S), while in the isolated patient, an apparently de novo heterozygous c.1183_1184insG truncating mutation was demonstrated in exon 10. All patients except one had bilateral reduced ocular anteroposterior axial length and a high hyperopic refractive error corresponding to posterior microphthalmos, features that have not been described as part of the disease. Our results suggest that posterior microphthalmos might be part of the clinical characteristics of Tietz/Waardenburg syndrome type 2A and expand both the clinical and molecular spectrum of the disease. © 2016 Wiley Periodicals, Inc.

Bilateral microphthalmos with cyst in a neonatal foal.

A 1-day-old miniature horse filly was presented to the University of Florida Veterinary Ophthalmology service for evaluation of multiple ocular anomalies which were present from birth. Protruding from the right orbit was a large, fluctuant, red, dry and variably ulcerated mass. A globe could not be appreciated clinically in the left orbit. Ocular ultrasound of both orbits was performed. This revealed a lobular, hypo-echoic structure filling the right orbit, with multiple hyperechoic septations; normal ocular structures were not identified. Ultrasound of the left orbit revealed a microphthalmic eye, with a well-defined, hyperechoic structure in the vitreous that was thought to be the lens. Due to irreversible blindness, the foal was humanely euthanized. Histopathology and immunohistochemistry of the orbital contents revealed bilateral microphthalmos with cyst, a congenital defect rarely reported in the veterinary literature.

Prosthodontic and surgical management of anophthalmia: a case report.

True Anophthalmos is an extremely rare condition and can cause psychological problems due to not only the absence of an eye but also from the disfigurement of the orbital socket and the eyelids. The present case shows the multidisciplinary approach in the treatment of a patient with anophthalmos. He needed an ocular plastic surgery for correct prosthesis insertion. The disfigurement caused by the loss of ocular content when restored with prosthesis maintains the facial symmetry there by improves the esthetics as well as anatomic and physiological function.

Posterior microphthalmos with retinal involvement related to MFRP gene: a report of 10 Brazilian patients.

BACKGROUND: To describe the phenotype and genotype of 10 Brazilian patients with variants in MFRP, posterior microphthalmos and retinal findings. METHODS: Complete ophthalmological evaluation was done at 4 different Brazilian centers. Genetic analysis was performed using commercial next generation sequencing panels for inherited retinal disorders. RESULTS: Ages of the patients ranged from 10 to 65 years and visual acuities from 0,05 to no perception of light. All were hyperopes (+4,25 to + 17,50) with a short axial length (14,4 mm to 18 mm). Common posterior segment features, though not present in all, were optic disc drusen (5/10), foveoschisis (5/10) and retinal pigmentary changes (8/10). Isolated patients presented with macular atrophy, serous retinal detachment, and chorioretinal folds. The most common variant in MFRP found in our patients was a deletion in exon 5 (c.498delC; p.Asn267Thrfs *25), present in all except 2 patients. Other variants found were c.523C>T (p.Gln175*), c.298delG (p.Ala100Argfs *37), c.666del (p.Thr223Argfs *83) and the novel variant c.257C>A (p.Ala86Asp). CONCLUSIONS: This is the first report of Brazilian patients with posterior microphthalmos and pathogenic variants in MFRP and the first describe of the variant p.Ala86Asp in literature. Our cases confirm the previously reported phenotype of high hyperopia, optic disc drusen, alterations in foveal architecture, retinal pigmentary changes with loss of photoreceptor function and visual field constriction. Report of such a rare condition is important to increase awareness to the phenotype of posterior microphthalmia with associated retinal conditions.

Novel compound heterozygous variants in LTBP2 associated with relative anterior microphthalmos.

PURPOSE: Relative anterior microphthalmos (RAM) is a rare congenital defect associated with severe vision impairment that is primarily caused by genetic alterations. The purpose of this study was to identify the causative genetic variants in two Chinese families with RAM with an autosomal recessive inheritance pattern. METHODS: DNA samples were obtained from two probands and their family members. Targeted next-generation sequencing (NGS) was used to screen 425 genes associated with inherited eye diseases to identify possible disease-causing variants in the two patients. Sanger sequencing was subsequently used to validate the results in both families. RESULTS: The targeted NGS panel identified potentially causative novel variants of the latent transforming growth factor beta binding protein 2 (LTBP2) gene in the two RAM families: a missense variant (c.2771C > T; p.Ala924Val) and an intronic variant (c.4582 + 9A > G) in Family A and a different missense variant (c.5239C > A; p.Arg1747Ser) and a synonymous variant (c.951G > A; p.Pro317Pro) in Family B. These four novel variants all cosegregated with the disease phenotype. CONCLUSION: To our knowledge, this is the first study to report novel LTBP2 gene variants related to RAM. Considering the importance of LTBP2 in ocular development, we provide initial insights into the potential pathogenic mechanisms of LTBP2 in RAM.

Insight into small eyes: a practical description from phenotypes presentations to the management.

This narrative review aimed to have an algorithmic approach to microphthalmos by a systematic search. The definition can be related to a number of special phenotypes. In the more challenging cases of complex microphthalmos, relative anterior microphthalmos, and nanophthalmos, the surgeon can approach these cases more safely if they have a deep understanding of the anatomical variations and ideal formulae for intraocular lens computation and knows how to avoid intra- and post-operative complications. In this article, we review the criteria by which we recognize and describe pre-, intra-, and post-operative considerations, as well as discuss the ideal intraocular lenses for microphthalmos, given the intricate varieties of small eye phenotypes.

Posterior Microphthalmos Pigmentary Retinopathy Syndrome.

Purpose: To report a case of a rare disease entity Posterior Microphthalmos Pigmentary Retinopathy Syndrome (PMPRS) in a 47-year-old female with a brief review of literature. Case Report: A 47-year-old woman presented with a history of defective vision with an associated difficulty in night vision. Clinical workup was done, which included a thorough ocular examination showing diffuse pigmentary mottling of fundus, ocular biometry showing short axial length with normal anterior segment dimensions, electroretinography showing extinguished response, optical coherence tomography showing foveoschisis, and ultrasonography showing thickened sclera-choroidal complex. Findings were consistent with those reported by other authors with PMPRS. Conclusion: Posterior microphthalmia with or without other ocular and systemic associations should be suspected in cases with high hyperopia. It is mandatory to carefully examine the patient at presentation and close follow-ups are needed to maintain visual function.

Microphthalmia, aphakia and agenesis of the optic chiasm and tract in a wild fox squirrel (Sciurusniger).

We describe gross and histopathological features of multiple ocular and neuro-ophthalmic abnormalities in a fox squirrel (Sciurus niger). Ophthalmic findings included severe bilateral microphthalmos, with the right eye more affected than the left. Histopathology confirmed severe microphthalmia, aphakia, disorganized retinal tissue and small optic nerves, as well as agenesis of the optic chiasm and optic tract. This combination of neuro-ophthalmic abnormalities has not been previously described in wild animals.

Retinal arcades in posterior microphthalmos: biometric correlation.

CLINICAL RELEVANCE: Posterior microphthalmos (PM) is a rare developmental disorder characterised by high hyperopia, short axial length, presence of retinal papillomacular fold and relatively normal anterior segment findings. BACKGROUND: The purpose of the study was to compare the retinal arcade distance from fovea between PM cases and to correlate axial shortening in PM eyes with imaging findings. METHODS: This retrospective, comparative case series included 24 eyes of 12 patients with PM as cases and an equal number of age- and sex-matched controls. Retinal findings on optical coherence tomography (OCT), OCT-angiography, Multicolour® image, axial length and corneal biometry were computed, compared and correlated between two groups. RESULTS: Retinal papillomacular fold was noted in all 24 PM eyes. Retinal arcade narrowing was noted in PM (p < 0.001). The central retina (p < 0.001) and choroid (p = 0.003) was thick in PM. Corneal biometry showed shorter axial length (p < 0.001), high keratometry readings (p < 0.001) and small corneal diameters (p = 0.011) in PM. Vessel density (p = 0.031) on OCTA was denser and foveal avascular zone area (p = 0.033) reduced in PM. Strong negative correlation of axial length with spherical equivalent (r = > -0.804;p < 0.001), vessel density (r = > -0.803; p = <0.001) and K1 (r = > -0.76; p < 0.001) and K2 (r = > -0.67; p = 0.001) keratometry readings was noted in PM. Significant positive correlation was noted between axial length and anterior chamber depth (r = 0.75; p < 0.001), foveal avascular zone area (r = 0.56; p = 0.033) and corneal diameter (r = 0.65; p = 0.001). Vessel density on OCT-angiography correlated positively with central corneal thickness (r = 0.552;p = 0.005) and corneal powers K1 (r = 0.709; p = 0.001) and K2 (r = 0.56; p = 0.004) and negatively with corneal diameter (r = > -0.521; p = 0.033). CONCLUSION: Increased choroidal thickening and retinal vascular arcade narrowing were two important, interesting observations noted with PM. Intercorrelation between the axial length, OCT, OCT-angiography and corneal biometry helped in understanding the pathogenesis and the structural and vascular changes in PM eyes.

Choroidal changes in posterior microphthalmos.

PURPOSE: To describe the choroidal variations in posterior microphthalmos (PM). METHODS: In this observational case series, four eyes of two patients diagnosed as PM based on the characteristic clinical features were included. Multimodal retinal imaging with clinical fundus documentation using ultrawide field fundus camera, optical coherence tomography (OCT) and indocyanine green angiography (ICGA) was done for these cases. RESULTS: Multimodal imaging of these cases confirmed the variations in the choroid in PM cases. In both cases, on OCT, the retina and choroid were thick. retinal papillomacular fold (RPMF) was noted in all four eyes. On ICGA, the dye transit time from the arm to choroid and retina were within normal limits. Choroidal vasculature in the far retinal periphery was reduced and was noted as hypocyanescent areas anterior to the equator while the density of choroidal vessels was significantly more posterior to the equator. Vortex veins were not visualised in both cases. CONCLUSION: Choroidal structure and vessels undergo alterations in PM. Further validation of these findings is required in a larger cohort of PM cases.

Recurrent Fetal Anophthalmia Caused by retinoids acid gene 6 mutations: Correlation between prenatal ultrasonography, magnetic resonance imaging, and pathology.

OBJECTIVE: Anophthalmia is an extreme form on the spectrum of anophthalmia-microphthalmia (A/M) syndrome. Most articles define fetal microphthalmia by an ocular diameter (OD) less than fifth percentile. Diagnosis of fetal microphthalmia using only orbital measurements such as interocular distance (IOD), and OD may neglect the presence or morphology of the fetal lens, hence failing to identify abnormalities of the fetal globe. CASE REPORT: We hereby present a case of isolated fetal anophthalmia in two consecutive pregnancies from the same mother. Both fetuses presented as full-sized globes with absence or small size of lens under fetal ultrasound examination. Magnetic resonance imaging and pathology of the second fetus further revealed a thorough view of the underdeveloped globes. Whole exon sequencing (WES) analysis for the parents-fetus trio revealed compound heterozygous mutations of the retinoids acid gene 6 (STRA6). CONCLUSION: Detailed examination for intraocular structures including fetal lens, in addition to orbital measurements by ultrasound is crucial for diagnosis of diseases in the A/M spectrum.

Posterior Microphthalmos Pigmentary Retinopathy Syndrome with Angle-Closure Glaucoma: A Case Report.

Purpose: To describe a particular form of posterior microphthalmos pigmentary retinopathy syndrome (PMPRS) with an atypical clinical presentation of pigment retinal dystrophy and an association to an inconstant complication which is angle-closure glaucoma (ACG). Methods: A 40-year-old male patient with ACG on maximal topical treatment was referred to our department for uncontrolled intraocular pressure. Best-corrected visual acuity was 2/10 in the right eye and light perception in the left eye. Intraocular pressure was 36 mmHg bilaterally. He had 360° peripheral anterior synechiae on gonioscopy. Fundus examination revealed total cupping with pale retinal lesions in both eyes and a few pigment deposits in the midperiphery of the right eye. Multimodal imaging was done. Results: Fundus autofluorescence revealed patchy areas of hypoautofluorescence. Optical coherence tomography (OCT) showed bilateral foveoschisis and macular folds. Anterior segment OCT showed a circumferential iridocorneal angle closure. Axial length measured with ultrasound biomicroscopy was 18.4 mm in the right eye and 18.1 in the left eye. Electroretinogram revealed attenuated scotopic responses. The patient was diagnosed with nanophthalmos-retinitis pigmentosa (RP)-foveoschisis syndrome complicated with ACG. A combined surgery with phacoemulsification - anterior vitrectomy - intraocular lens implantation and trabeculectomy was performed in both eyes with a satisfactory outcome. Conclusions: In its typical forms, PMPR syndrome is an association of nanophthalmos - RP - foveoschisis and optic nerve head (ONH) drusen. Incomplete phenotypes may lack ONH drusen or foveoschisis. Patients with PMPRS have to be screened for iridocorneal angle synechia and ACG.

Three Novel Mutations of Microphthalmos Identified in Two Chinese Families.

Genetic alterations are a major cause of microphthalmos, while novel-related genes and mutations in microphthalmos have rarely been explored. To identify the underlying genetic defect responsible for microphthalmos eyes in two three-generation Chinese families, we screened 425 genes involved in common inherited non-syndromic eye diseases with next-generation sequencing-based target capture sequencing of the two probands of two three-generation Chinese families diagnosed with microphthalmos. Variants were filtered and analyzed to identify possible disease-causing variants before Sanger sequencing validation. We enrolled two families with microphthalmos (Family 1: microphthalmos with congenital ocular coloboma and Family 2: simple microphthalmos). Two novel heterozygous mutations, Peroxidasin (PXDN) c.3165C>T (p.Pro1055Pro) and PXDN c.2640C>G (p.Arg880Arg), were found in Family 1, and Crystallin Beta B2 (CRYBB2) c.481G>A (p.Gly161Arg) was found in Family 2, but none of the mutations were found in the unaffected individuals, who were phenotypically normal. Multiple orthologous sequence alignment (MSA) revealed that the CRYBB2 p.Gly161Arg mutation was a deleterious effect mutation. In conclusion, the three novel mutations found in our study extend our current understanding of the genetic basis of microphthalmos and provide early pre-symptomatic diagnosis and emphasize the significance of genetic diagnosis of microphthalmos.

Endoscopy-assisted pars plana lensectomy for brunescent cataracts in eyes with microcornea with microphthalmos.

PURPOSE: Conventional cataract surgeries can be a challenge in eyes with microcorneas due to difficult manipulation in a crowded anterior chamber (AC) and can lead to a high occurrence of corneal edema and an increased rate of complications. Similarly, in cases of dense brunescent cataracts even a lensectomy through posterior approach may prove to be difficult because of inadequate visualization. An endoscopyassisted pars plana lensectomy can help in obviating these difficulties. This study aims to describe the surgical technique of endoscopy-assisted pars plana lensectomy in eyes with brunescent cataract, microcornea, and microphthalmos. METHODS: Retrospective review of two cases where endoscopy-assisted pars plana vitrectomy and lensectomy was performed for patients with dense cataract and microcornea and microphthalmos. RESULT: Complete clearance of the cataract was achieved without having to resort to a sclerocorneal incision. Postoperatively the cornea was clear and there was no postoperative corneal edema. CONCLUSION: Endoscopy-assisted pars plana lensectomy can help in overcoming the challenges of conventional anterior and posterior approaches of cataract extraction in cases of microcornea with reduced intraoperative and postoperative complications.