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

PURPOSE: 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. METHODS: 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: 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. CONCLUSION: 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.

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

PURPOSE: To evaluate axial length (AL), orbital width (OW) and height (OH) development in congenital microphthalmia and anophthalmia (MICA) using serial ultrasonography measurements. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Workflow and treatment results for computer-aided design and 3D-printed conformer therapy of congenital anophthalmia and microphthalmia.

BACKGROUND/AIMS: To evaluate treatment with custom, three-dimensional (3D) printed conformers for socket expansion in congenital microphthalmia and anophthalmia (MICA). METHODS: Retrospective analysis of prospective cohort from 2016 to 2020. All children received custom-made 3D-printed conformers increasing in size. We measured height, width, thickness, surface and volume of first and consecutive conformers, as well as horizontal palpebral fissure length (HPF) at start and follow-up visits. We analysed these parameters for severely (<45%) and moderately (>45%-75%) affected children, based on affected axial length on ultrasonography. RESULTS: We included 18 cases (9 severe, 9 moderate) with a total of 174 conformers (88 severe, 86 moderate) and a mean follow-up of 2.8 years (range 1.3-4.8). The mean relative HPF increased from 77% to 93% with 16/17 cases reaching >80%, and 12/17 cases >90% symmetry. Horizontal and vertical conformer dimensions increased up to 10 months of treatment, with a steeper slope for the severe group (10.5% vs 5.5% for height and 9.0% vs 6.1% for width gain per treatment month, for severe and moderate MICA, respectively). After 10 months of treatment conformer height and width increased only slightly. No serious complications were observed. CONCLUSION: 3D-design and printing of solid conformers results in highly acceptable horizontal eyelid symmetry in the treatment of congenital MICA. The mean increase in conformer height and width in the first 10 months should be about 170% for moderate and about 200% for severe MICA. The presented conformer size formulas can aid ophthalmologists and ocularists to plan conformer treatment.

Meta-analysis of ocular axial length in newborns and infants up to 3 years of age.

In pediatric ophthalmology it is often necessary to obtain axial length in young children. For children older than 3 years, noncontact biometry can be used. For younger children this is usually not an option, and the clinician needs to rely on other imaging modalities. Depicted data curves in textbooks elaborate on few studies and limited number of subjects. The existing literature regarding normal axial length for preterm infants and term newborns is summarized and critically appraised for number of subjects, relevance, measurement method and error, gender and retinopathy of prematurity. We obtained axial length measurements for a total number of 6,575 eyes in 27 papers published from 1964 to 2018 (9 papers with 2,272 eyes for preterm children, 24 papers with 4,303 eyes for term children). Initially, axial length increases rapidly: from a mean 5.1-16.2 mm in week 12 to week 37 gestational age. From 38 weeks, growth rate decreases from 16.2 mm to a mean of 21.8 mm at 3 years old. Male infants have a larger average axial length than females at birth; the difference is 0.24 mm (95%CI: 0.15-0.33, P < 0.001). We present a useful growth curve and formula that may serve as a reference for diagnosing abnormal growth.

Impact of Bevacizumab on Visual Function, Tumor Size, and Toxicity in Pediatric Progressive Optic Pathway Glioma: A Retrospective Nationwide Multicentre Study.

BACKGROUNDS: Bevacizumab (BVZ) is used as a subsequent line of treatment for pediatric optic pathway glioma (OPG) in the case of progression. Data on the treatment effect concerning tumor progression and visual function are scarce and nationwide studies are lacking. METHODS: We performed a retrospective, nationwide, multicentre cohort study including all pediatric patients with OPG treated with BVZ in the Netherlands (2009-2021). Progression-free survival, change in visual acuity and visual field, MRI-based radiologic response, and toxicity were evaluated. RESULTS: In total, 33 pediatric patients with OPG were treated with BVZ (median 12 months). Visual acuity improved in 20.5%, remained stable in 74.4%, and decreased in 5.1% of 39 of all analysed eyes. The monocular visual field improved in 73.1%, remained stable in 15.4%, and decreased in 7.7% of 25 analysed eyes. Radiologic response at the end of therapy showed a partial response in 7 patients (21.9%), minor response in 7 (21.9%), stable disease in 15 (46.9%), and progressive disease in 3 (9.3%). Progression-free survival at 18 and 36 months after the start of BVZ reduced from 70.9% to 38.0%. Toxicity (≥grade 3 CTCAE) during treatment was observed in five patients (15.2%). CONCLUSION: Treatment of BVZ in pediatric patients with OPG revealed stabilisation in the majority of patients, but was followed by progression at a later time point in more than 60% of patients. This profile seems relatively acceptable given the benefits of visual field improvement in more than 70% of analysed eyes and visual acuity improvement in more than 20% of eyes at the cessation of BVZ.

Three-Dimensional Computer-Aided Design of a Full-Color Ocular Prosthesis with Textured Iris and Sclera Manufactured in One Single Print Job.

Three-dimensional (3D) printing of ocular prosthesis has been scarcely described in medical literature. Although ocular prostheses have been 3D printed successfully, iris colors are often manually added to the final product afterward. The objective was to produce a 3D-printed ocular prosthesis with textured iris and sclera in one single print job. We designed an average 3D model of an ocular prosthesis in 3D software, and took a high-resolution digital photograph of a human eye, which was processed in graphical software. By using functions called "displacement mapping" and "UV mapping" on the 3D model, the extent of height displacement was used to digitally produce a textured and colored iris and sclera on the 3D model. By using a polyjet 3D printer, different colors and materials could be used for different prosthesis components. We were able to design and 3D print a lifelike ocular prosthesis with realistic iris and sclera texture. The process took less than 4 h, of which 2.5 h are "printing time," reducing labor time compared with conventional methods. This proof-of-concept adds valuable knowledge to the future manufacture of 3D-printed ocular prostheses, which has several benefits over the conventional production method: 3D printing is much faster, reproducible, and prostheses can easily be digitally adjusted and reprinted. This study is an important step in the development of a full-fledged 3D workflow to produce lifelike custom eye prostheses.

Classification for treatment urgency for the microphthalmia/anophthalmia spectrum using clinical and biometrical characteristics.

PURPOSE: Current clinical classifications do not distinguish between the severity of the MICrophthalmia/Anophthalmia (MICA) spectrum with regard to treatment urgency. We aim to provide parameters for distinguishing mild, moderate and severe MICA using clinical and biometrical characteristics. METHODS: We performed a single-centre, cross-sectional analysis of prospective cohort of 58 MICA children from September 2013 to February 2018 seen at the Amsterdam University Medical Center, The Netherlands. All patients with a visible underdeveloped globe were included. We performed full ophthalmic evaluation including horizontal palpebral fissure length, axial length by ultrasound and/or MRI measurements, paediatric and genetic evaluation. Cases were subdivided based on clinical characteristics. Biometrical data were used to calculate the relative axial length (rAL) and the relative horizontal palpebral fissure length (rHPF) compared with the healthy contralateral eye for unilateral cases. RESULTS: In previously untreated patients, a strong correlation exists between rAL and rHPF, distinguishing between severe, moderate and mild subjects using rAL of 0-45%, 45-75% and 75%-100%, respectively. Clinical subgroups were randomly dispersed throughout the scatterplot. CONCLUSION: Current classifications lack clinical implications for MICA patients. We suggest measuring eyelid length and axial length to classify the severity and determine treatment strategy. The 'severe' group has obvious asymmetry and abnormal socket configuration for which therapy should quickly be initiated; the 'moderately' affected group has normal socket anatomy with a microphthalmic eye with disturbing asymmetry for which treatment should be initiated within months of development; the 'mild' group has a slightly smaller axial length or less obvious eyelid asymmetry for which reconstructive correction is possible, but expansive conformer treatment is unnecessary.