UNASSIGNED: Chandler syndrome (CS) is one of the iridocorneal endothelial syndromes (ICEs) with proliferation of abnormal corneal endothelial cells over the anterior chamber (AC) angle and iris, resulting in complications, for example, secondary angle closure glaucoma (SACG). We report an association between CS and nanophthalmos, highlighting diagnostic and therapeutic challenges and pathological insights.
UNASSIGNED: A 46-year-old female patient presented with bilateral progressive blurring of vision. Examination revealed bilateral (OU) small corneal diameter, shallow AC, closed AC angle, beaten-bronze appearance of corneal endothelium, and mild iris atrophy in the right eye (OD). Intraocular pressure was 48 mm Hg and 22 mm Hg in the OD and left eye (OS), respectively. Fundus examination revealed optic nerve head cupping. Biometry showed short axial length and microcornea OU, that is, nanophthalmos. Optical coherence tomography and visual field revealed structural and functional evidence of glaucomatous optic neuropathy. Specular microscopy demonstrated reduction of corneal endothelial cell density and the light-dark reversal characteristic of ICE. Therefore, a diagnosis of CS with SACG and nanophthalmos was made. The patient was referred to a specialized glaucoma center with recommendation of clear lens extraction and a glaucoma drainage device with retropupillary tube placement.
UNASSIGNED: This is the first report of an association between CS and nanophthalmos. It highlights the possibility of SACG despite evident risk factors for primary angle closure glaucoma (PACG). Furthermore, it provides a hypothesis about the etiology of ICE. The concurrence of CS and nanophthalmos suggests that a common developmental mechanism could be implicated since periocular mesenchyme, the embryological precursor of corneal endothelium, plays a role in the development of optic cup and stalk.
UNASSIGNED: SACG should be considered even in the presence of evident risk factors for PACG, such as nanophthalmos. Additionally, the association of nanophthalmos and CS warrants revisiting the yet inconclusive etiology of CS, where a developmental mechanism could be considered.
UNASSIGNED: Ameen Ismail A, El-Ruby SA. Bilateral Chandler Syndrome, Nanophthalmos, and Angle Closure Glaucoma: A Complex Presentation, Challenging Diagnosis, and Pathological Insight-A Case Report. J Curr Glaucoma Pract 2024;18(2):68-73.

Nanophthalmos, characterized by an abnormally small ocular globe, presents significant challenges in the management of strabismus due to its unique anatomical constraints. This detailed case report highlights the intricacies and outcomes of strabismus surgery in a patient with nanophthalmos, providing valuable insights into the surgical considerations and adaptations required for this rare condition. The subject of this case, a young girl diagnosed with esotropia and high hyperopia, underwent unilateral medial rectus muscle recession in an attempt to correct her esotropia. Despite the careful surgical approach and postoperative management, a two-year follow-up revealed a limited response to the intervention, with improvements in visual acuity but continued presence of esotropia and lack of stereopsis development. This case sheds light on several key considerations in the surgical treatment of strabismus in nanophthalmos patients, including the potential for reduced surgical effectiveness due to the small globe size, the importance of accurate preoperative assessment, and the challenges in predicting surgical outcomes. Additionally, it discusses the implications of these findings for future surgical planning, the potential need for revision surgeries, and the broader research context, emphasizing the necessity for a deeper understanding of the biomechanical and anatomical particularities of nanophthalmos in the context of strabismus surgery. The report concludes with recommendations for improving surgical strategies and patient outcomes, advocating for more comprehensive studies and a tailored approach to treating strabismus in individuals with nanophthalmos.

UNASSIGNED: Nanophthalmos is a congenital ocular structural anomaly that can cause significant visual loss in children. The early diagnosis and then taking appropriate clinical and surgical treatment remains a challenge for many ophthalmologists because of genetic and phenotypic heterogeneity. The objective of this study is to identify the genetic cause of nanophthalmos in the affected families and analyze the clinical phenotype of nanophthalmos with MFRP gene variation (Microphthalmia, isolated; OMIM#611040 and Nanophthalmos 2; OMIM#609549, respectively).
UNASSIGNED: Comprehensive ophthalmic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. The normal protein structure was constructed using Alphafold. Mutant proteins were visualized using pymol software. Pathogenicity of identified variant was determined by in silico analysis and the guidelines of American College of Medical Genetics and Genomics (ACMG). The relationship between genetic variants and clinical features was analyzed.
UNASSIGNED: Five nanophthalmos families were autosomal recessive, of which four families carried homozygous variants and one family had compound heterozygous variants in the MFRP gene. Both family one and family three carried the homozygous missense variant c.1486G>A (p.Glu496Lys) in the MFRP gene (Clinvar:SCV005060845), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis. The proband of family one presented papilloedema in both eyes, irregular borders, thickened retinas at the posterior pole, tortuous and dilated retinal vessels, and indistinguishable arteries and veins, while the proband of family three presented uveal effusion syndrome-like changes in the right eye. In families one and 3, despite carrying the same gene variant, the probands had completely different clinical phenotypes. The homozygous nonsense variant c.271C>T (p.Gln91Ter) (Clinvar:SCV005060846) of the MFRP gene was detected in family 2, presenting shallow anterior chamber in both eyes, pigmentation of peripheral retina 360° from the equator to the serrated rim showing a clear demarcation from the normal retina in the form of strips. Family four proband carried the homozygous missense variant c.1411G>A (p.Val471Met) in the MFRP gene (Clinvar:SCV005060847), family five proband carried compound heterozygous missense variants c.1486G>A (p.Glu496Lys) and c.602G>T (p.Arg201Leu) in the MFRP gene (Clinvar:SCV005060848), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis, and they all presented clinically with binocular angle-closure glaucoma, family four also had retinal vein occlusion in the right eye during the follow-up.
UNASSIGNED: In this study, pathogenic variants of the MFRP gene were detected in five nanophthalmos families, including two novel variants. It also revealed a distinct phenotypic diversity among five probands harboring variants in the MFRP gene. Our findings extend the phenotype associated with MFRP variants and is helpful for ophthalmologists in early diagnosis and making effective treatment and rehabilitation strategies.

OBJECTIVE: Patients with nanophthalmos might be prone to developing intraocular inflammation following an acute glaucoma attack. Here, we aimed to investigate the role of MYRF in intraocular inflammation by modeling the mutation in mice.
METHODS: Nanophthalmos frameshift mutation of Myrf was introduced into the mouse genome with the CRISPR-Cas9 system. Signaling pathways in eye tissues were delineated using RNA sequencing and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Intraocular inflammation was induced by a lipopolysaccharide (LPS) intravitreal injection. Dexamethasone (DEX) was administered systemically and locally a week before the LPS injection. The anterior segment clinical scores of the mice were examined 24 h after the LPS injection. Infiltrating inflammatory cells were evaluated with histopathology and immunofluorescence. The mRNA levels of inflammatory cytokines were quantified with reverse transcription-quantitative PCR (RT-qPCR) and the corresponding protein concentrations using enzyme-linked immunosorbent assay (ELISA).
RESULTS: Many inflammation-associated signaling pathways were enriched in Myrf mut/+ mice ocular tissues. Clinical scores of Myrf mut/+ mice were significantly higher than those of Myrf +/+ mice 24 h after LPS administration. Histological examination demonstrated high inflammatory cell infiltration in the anterior and vitreous chambers in Myrf mut/+ mice, with numerous CD45+ and CD11b+ inflammatory cells. Moreover, enhanced expression of inflammatory cytokines MCP-1, TGF-β, and IL-1β in eyes and aqueous humor of Myrf mut/+ mice was detected. Remarkably, pretreating Myrf mut/+ mice with DEX relieved the intraocular inflammation.
CONCLUSIONS: Nanophthalmos-associated MYRF mutation renders mouse eyes more susceptible to inflammation. Dexamethasone treatment ameliorates the inflammatory response.

UNASSIGNED: Nanophthalmos is characterized by a short axial length, a thick choroid, and a thick sclera. Unilateral symptomatic disc swelling in nanophthalmos presents both a diagnostic and a therapeutic challenge.
UNASSIGNED: A healthy 59-year-old man reported a two-week-long abrupt vision reduction in his right eye. 20/100 best spectacle (+17.25 diopter) corrected visual acuity, unilateral widespread disc enlargement, central scotoma, and a slight color vision disruption without an afferent pupillary defect were among the positive findings in the right eye. Workup for neuro-ophthalmology was negative. Numerous consultations did not suggest any form of treatment for the patient. Review of the optical coherence tomography (OCT) indicated a small, crowded optic nerve head and substantial diffuse choroidal thickening with dome-shaped temporal peripapillary area with choroidal expansion. In addition to circumferential anterior four-quadrant 95%-deep sclerectomy from recti insertion to the vortices, radial nasal posterior sclerotomy reaching the optic nerve sheath was performed on the patient. After the procedure, 2 weeks later, the patient\'s vision returned, and it persisted until the 6-month follow-up. By OCT, the two eyes were comparable as far as disc contour and nerve fiber layer thickness.
UNASSIGNED: This form of sclerectomy, which aims at decompressing the oncotic choroidal pressure, is an effective treatment for compressive optic neuropathy in the context of nanophthalmos. Could sclerectomy assist in treating other optic neuropathies associated with peripapillary pachychoroid?

Purpose:To describe the visual outcomes and problems that resulted from surgical treatment of nanophthalmic complete retinal detachment (RD) with retina-lens contact. Methods: A multicenter retrospective case series with deep sclerectomy as a treatment was performed. Results: Five cases had extensive deep sclerectomies, 3 with intended drainage of subretinal fluid (SRF). The RD resolved 1 week postoperatively in 4 cases and within 1 month in 1 case. The visual acuity improved from light perception to a median of 20/100. Three cases had longstanding lens touch beyond 1 year and improved VA to 20/100, 20/150, and hand motions, respectively. Complications included focal lens dialysis in 2 cases (passive drainage of SRF) and lens or intraocular lens dislocation in 1 case each (active drainage of SRF). Ultrasound biomicroscopy and anterior optical coherence tomography showed a very narrow angle and short zonules. Conclusions: Deep sclerectomy results in good anatomic and functional improvements in advanced cases of nanophthalmos exudative detachment, which is often considered to be incurable.

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.

UNASSIGNED: Though patients with nanophthalmos frequently endure decreased quality of vision with contact lenses or spectacles, refractive surgery is generally an inadequate alternative due to the associated high refractive error. A refractive lens exchange (RLE) is an alternative option but is technically challenging, requiring accuracy in biometry measurements and procedures.
UNASSIGNED: This case discusses a 27-year-old female with nanophthalmos (axial lengths 17.6 mm and 17.4 mm, right and left eyes, respectively) who underwent a femtosecond laser-assisted (FLA) RLE with simultaneous implantation of a monofocal and a Sulcoflex trifocal (Rayner, Britain) lens in each eye. Preoperative cycloplegic refraction was +11.50/-0.75 × 145 and +12.00/-1.00 × 35 in the RE and LE, respectively. Best-corrected visual acuity (BCVA) at distance and near in the RE and LE was 6/7.5 and J1, 6/8.5 and J2, respectively. Uncorrected visual acuity (UCVA) was >6/120 and >J14 for each eye. FLA RLE was performed in the RE, then in the LE 2 weeks later. In each eye, a monofocal (44.0 D, RE, and LE) and a Sulcoflex trifocal lens (both implants, Rayner, Britain) were implanted in one procedure. Distance and near UCVA measured 6 weeks post-op RE and 1-month post-op LE at 6/8.5 and J1 in the RE, 6/10 and J1 in the LE. The RE and LE refraction and BCVA were +0.50/-1.00 × 115, 6/7.5, and plano/-1.00 × 55, 6/8.5, respectively. The post-op outcomes were uneventful.
UNASSIGNED: A single procedure concurrently implanting a monofocal and Sulcoflex trifocal intraocular lens in nanophthalmic eyes resulted in an excellent UCVA. This procedure can be considered esthetic and reconstructive as it significantly improves patient appearance and function.

BACKGROUND: We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine.
METHODS: A 42-year-old male patient with nanophthalmos experienced sudden blurred vision in the right eye after using topical brimonidine when picking up tennis balls repeatedly 6 weeks after bilateral YAG peripheral iridotomy. Ocular examination showed wide choroidal and exudative retinal detachment in the temporal and inferior region, involving the macula. Acute uveal effusion in the right, bilateral nanophthalmos was diagnosed. Oral and topical corticosteroids, combined with topical nonsteroids and atropine led to a complete resolution of the uveal effusion after one month.
CONCLUSIONS: This case suggested a possible causal relationship between the topical use of brimonidine and acute uveal effusion in patients with nanophthalmos. Topical brimonidine should be used with caution in nanophthalmic eyes.

Nanophthalmos is a rare congenital condition of the eyeball that is characterised by a smaller size of the anterior and posterior segments without associated ocular malformations. Typical features that have traditionally been described in these eyes are short axial length, thickened sclera, cornea with a smaller diameter, narrow anterior chamber, and an increased lens to globe volume ratio. However, at present, there is still a lack of recognised diagnostic criteria for nanophthalmos and a classification of its severity. Its clinical relevance stems from the increased risk of multiple ocular conditions, such as high hyperopia, amblyopia, angle-closure glaucoma, retinal detachment, and cataracts. Likewise, in relation to surgery in these eyes, there are particularities in cataract and glaucoma surgery and with a greater risk of associated intra- and postoperative complications. In this way, the treatment of nanophthalmos focuses on controlling the associated eye conditions and reducing and controlling surgical complications. This review aims to update what has been published in recent years regarding nanophthalmos.