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.

An Individualized 3-Dimensional Designed and Printed Conformer After Dermis Fat Grafting for Complex Sockets.

PURPOSE: To introduce a novel technique to design individually customized conformers for postenucleation sockets with dermis fat implants. METHODS: We use a 3-dimensional scan of the frontal face/orbit and eyelid contour to design an individualized conformer. This polymethylmetacrylate printed conformer is adapted to patients' socket, palpebral fissures, horizontal eyelid aperture, curvature of the eyelids, and mean diameter of patients' contralateral eye. Sutures through holes in the inferior part of the conformer and in the extension can be placed to fixate the conformer and anchor fornix deepening sutures. RESULTS: A correct fitting conformer can be printed and attached to the socket and eyelids. The shape of this conformer can be used subsequently postsurgically to design the ocular prosthesis. CONCLUSION: Presurgical planning is important to anticipate for a functional socket to adequately fit an artificial eye. The presented technique using 3-dimensional imaging, designing, and printing promises to prevent conformer extrusion and forniceal shortening.

A Novel Method to Measure Artificial Eye Motility.

PURPOSE: To measure objectively, reproducibly, and noninvasively artificial eye motility, a fundamental aspect in the (cosmetic) outcome of enucleation. METHOD: A gaze- and pupil-tracking system, the "iView X," was implemented to measure horizontal eye motility. The system, with adjusted software, was tested with patients wearing 1 prosthetic eye after enucleation for retinoblastoma. Measurements were repeated 5 times in every patient and analyses were performed twice by 2 independent observers. Reproducibility was tested via linear mixed models. After the implementation of the method, more data were obtained, including more patients with a history of enucleation for the treatment of retinoblastoma for eye tracker measurement, and differences in motility percentages between implant types and sizes were analyzed via Mann-Whitney U tests. RESULTS: The intraclass correlation coefficient of the interobserver variable in the patient test group (n = 27, 6-53 years) was 0.98 and 0.96 for measurement of left gaze and right gaze, respectively. Intraobserver variation was <0.001. In the total of 58 included patients for comparative analysis, mean difference of prosthesis motility compared with the contralateral eye in abduction was 57.1% (range 3.2-91.5%); in adduction 65.8% (range 24.0-92.0%). No statistical differences were found between the different implant types and sizes. CONCLUSION: Motility measurements of the prosthetic eye in comparison to the contralateral eye using the iView X system are reproducible and reliable. This is, to the authors' knowledge, the first easy applicable, noninvasive, reproducible, and commercially available instrument to evaluate prosthesis motility. With the adjusted software program (freely available on request), a similar objective measurement can be performed worldwide. The implant size or type did not influence the outcome of the motility measurement; this finding deserves additional study.

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.

Effects of orbital decompression on duction, cyclotorsion and diplopia.

BACKGROUND: Orbital decompression is commonly performed to correct proptosis in patients with Graves' orbitopathy (GO). In literature, the incidence of new-onset constant diplopia after orbital decompression varies. Few studies have evaluated changes in duction and cyclodeviation after orbital decompression. We evaluated the changes in duction, cyclodeviation, eye position and degree of diplopia after orbital decompression. METHODS: We retrospectively analysed data from patients who underwent orbital decompression at our hospital between January 2016 and July 2020. Data regarding the type of decompression, eye position, duction, cyclodeviation and level of diplopia according to the Gorman score were recorded. RESULTS: Data from 281 eyes/orbits of 156 patients were analysed. Proptosis decreased from 23.8±2.5 to 20.9±2.5 mm. Horizontal and vertical duction range decreased (horizontal d=0.40 and vertical 0.30; p=0.000) after surgery; however, the change was not clinically significant (≤5°). Horizontal deviation changed towards esodeviation (d=-0.45; p=0.000), whereas vertical deviation remained stable (d=0.15; p=0.161). Preoperative cyclotorsion in the primary and downgaze positions changed towards incyclodeviation (primary: d=0.30, p=0.021; downgaze d=0.30, p=0.039). Diplopia improved in 22% (18 patients), whereas new-onset constant diplopia developed in 11% (12 patients). Elevation has an excellent predictive value of causing new-onset constant diplopia when measured preoperatively as <19°, sensitivity 88.0%, specificity 41.7% (area under the curve 0.812 (95% CI 0.660 to 0.963); p=0.000). CONCLUSION: After orbital decompression, incidence of new-onset constant diplopia was 11% and 22% of the patients had partial or complete improvement of their diplopia. The changes in duction, cyclodeviation and horizontal deviation showed a statistical but not clinical difference. Patients with GO and a preoperatively restricted elevation of <19° are at risk of developing new-onset constant diplopia. In addition, preoperative incyclodeviation may worsen after decompression surgery.

[Watery eyes: diagnostic and therapeutic considerations]. / Tranende ogen.

Tear complaints can arise from either an increased tear production or from a disturbed tear drainage. Increased tear production from the lacrimal gland is a neuroregulated response to a dried out or irritated ocular surface. Dryness often results from a reduced quality of the tear film, but can also be caused by eyelid malposition with increased globe exposure. Impaired tear drainage usually occurs when the lacrimal drainage system is blocked at the level of the ductus nasolacrimalis, the canaliculi or the lacrimal punctae. Anatomical knowledge of the lacrimal system is necessary to distinguish between the different causes. Using cases and illustrations, we provide insight into the diagnostic considerations for a patient with a watery eye.

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.

Recurrent contracted sockets treated with personalized, three-dimensionally printed conformers and buccal grafts.

PURPOSE: Recurrent contracted sockets are complex situations where previous surgeries have failed, disabling the wear of an ocular prosthesis. A combined method of surgery and long-term fixation using custom-made, three-dimensional (3D) printed conformers is evaluated. METHODS: Retrospective case series of nine patients with recurrent excessive socket contraction and inability to wear a prosthesis, caused by chemical burns (n = 3), fireworks (n = 3), trauma (n = 2) and enucleation and radiotherapy at childhood due to optic nerve glioma (n = 1) with three average previous socket surgeries (range 2-6). Treatment consisted of a buccal mucosal graft and personalized 3D-printed conformer designed to be fixated to the periosteum and tarsal plates for minimal 2 months. Primary outcome was the retention of an ocular prosthesis. Secondary outcome was the need for additional surgeries. RESULTS: Outcomes were measured at final follow-up between 7 and 36 months postoperatively (mean 20 months). Eight cases were able to wear an ocular prosthesis after 2 months. Three cases initially treated for only the upper or only the lower fornix needed subsequent surgery for the opposite fornix for functional reasons. Two cases had later surgery for cosmetic improvement of upper eyelid position. Despite pre-existing lid abnormalities (scar, entropion, lash deficiency), cosmetic outcome was judged highly acceptable in six cases because of symmetric contour and volume, and reasonably acceptable in the remaining two. CONCLUSIONS: Buccal mucosal transplant fixated with a personalized 3D-designed conformer enables retention of a well-fitted ocular prosthesis in previously failed socket surgeries. Initial treatment of both upper and lower fornices is recommended to avoid subsequent surgeries for functional reasons.

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.

Search for a correlation between telomere length and severity of retinitis pigmentosa due to the dominant rhodopsin Pro23His mutation.

PURPOSE: Great variation exists in the age of onset of symptoms and the severity of disease at a given age in patients with retinitis pigmentosa (RP). The final pathway for this disease may involve apoptotic photoreceptor cell death. Telomere length is associated with biologic aging, senescence, and apoptosis. We evaluated whether the length of telomeres in leukocytes correlated with the severity of RP in patients with the Pro23His rhodopsin mutation who have shown marked heterogeneity in disease severity. METHODS: We evaluated 122 patients with the Pro23His rhodopsin mutation. The patients' retinal function was stratified according to their 30-Hz cone electroretinogram (ERG). The length of telomeres in leukocytes was measured by the quantitative real time polymerase chain reaction (qRT-PCR) method in the 15 patients with the highest age-adjusted 30-Hz ERG amplitudes and in the 15 patients with the lowest amplitudes. RESULTS: Mean leukocyte telomere length was similar in the 15 patients with the highest cone ERG amplitudes (median: 0.40 units; interquartile range 0.36-0.56) and the 15 patients with the lowest cone amplitudes (median: 0.41 units; inter quartile range 0.34 -0.64; p=0.95). CONCLUSIONS: We found no evidence for an association between telomere length and the severity of RP as monitored by the cone ERG in patients with the Pro23His rhodopsin mutation.

Cosmetic results of enucleation and/or external beam radiation therapy in 195 retinoblastoma survivors.

PURPOSE: To report the cosmetic outcome and late effects of enucleation and/or irradiation for retinoblastoma and to evaluate the role of orbital implants. METHODS: Patients (age >4 years) enucleated and/or irradiated for retinoblastoma, visiting the hospital for routine follow-up (April 2013 to May 2015), were included in our cross-sectional study. Data were obtained via clinical records, questionnaires, physical measurements and standardized photographs. Two independent observers scored the cosmetic features: upper eyelid position, lower eyelid position, volume deficiency, and prosthesis motility and overall cosmetic appearance. RESULTS: A total of 195 patients participated. Ptosis was seen in 45 (28.3%) patients, lower lid sagging in 45 (28.3%). Both complications were associated with the orbital implant; ptosis being more common with increasing implant size (5.6% without implant, 16.7% with small implant, 37.1% with medium implant and 76.9% with large implant) and lower lid sagging being more common in patients without implant (20% with implant versus 37.5% without). Volume loss of the superior sulcus was seen in 107 sockets (66.9%), most frequent in additionally irradiated patients (χ2 (2) = 42.7, p < 0.001) and in patients without implant (χ2 (2) = 11.92, p = 0.003). Prosthesis motility was better in patients with orbital implant, regardless of the size. CONCLUSION: Minor late and potentially treatable effects were seen in patients with implant. Larger sized implants were associated with a higher incidence of ptosis; implant size did not affect subjective outcome with respect to volume or prosthetic motility. Treatment with EBRT had a less favourable outcome.

Persistent socket pain postenucleation and post evisceration: a systematic review.

PURPOSE: To investigate causes, diagnostics and treatment modalities for persistent socket pain (PSP) after enucleation and evisceration. METHODS: A systematic search was undertaken in accordance with the PRISMA Statement, in PubMed, Embase.com and Thomson Reuters/Web of Science. We searched for relevant papers until the 28th of July 2016. Inclusion criteria were (1) patients with a history of enucleation or evisceration, (2) PSP, (3) report of the cause and/or used diagnostics and/or treatment modality, (4) full text in English, Dutch or Spanish language. Excluded were (1) review articles, (2) comments, and publications concerning, (3) nonhumans, (4) exenterated patients, (5) acute postoperative pain, or (6) periorbital pain without pain in the socket. Given the lack of high quality evidence from randomized controlled trials, we examined all available evidence from primary observational studies and assessed quality within this lower level of evidence. RESULTS: A total of 32 studies were included. Causes of PSP found were prosthesis-related (n = 5), dry socket (n = 2), trochleitis (n = 3), compression of the trigeminal nerve (n = 2), implant-related (n = unknown), inflammation (n = 5), surgery-related (n = 4), neuromas (n = 8), malignant tumours (n = 3), psychiatric/psychosocial (n = 2), phantom pain (n = 149), rarer entities (n = 3) or unknown (n = 14). Nonsurgical treatments suffice for conditions as trochleitis, prosthesis-related pain, dry socket and for phantom pain. Other causes of pain may require more invasive treatments such as implant removal. CONCLUSION: Careful history and examination can give some direction in the diagnostic procedure; however, PSP is probably multifactorial and the specific origin(s) may remain uncertain. Implant replacement can be an effective treatment. Studies to identifiy less invasive procedures are required.

Case series: effect of dermis-fat implants in different late onset socket problems encountered in retinoblastoma patients.

BACKGROUND: Cosmetic dissatisfaction, pain, and chronic discharge may present months till years after enucleation in patients operated because of retinoblastoma. If noninvasive treatment modalities are insufficient, socket reconstruction can be considered. In this study, we discuss the results of dermis-fat exchange to treat these problems. METHOD: Four patients with late onset post enucleation socket problems with a request for treatment were included in this prospective study. Socket inspection was documented and pictures at baseline and at a follow-up of at least 6 months were taken. To quantify the problem 'pain', a VAS score at baseline and at follow up was used. For the problem 'cosmetic dissatisfaction' standardized questionnaires were used. RESULTS: Two patients were included because of cosmetic dissatisfaction; one was included with chronic pain and one with chronic discharge. Reconstruction of the socket using autologous dermis-fat insertion was done in all four. In one of them, severe shrinking of the fat developed. This patient was treated with additional injectable fillers. Both of them, ultimately, had satisfactory results. Autologous fat transplantation also solved the problem of chronic discharge and pain in the two other patients. CONCLUSION: Socket reconstruction by autologous dermis-fat exchange may solve different post enucleation socket problems. However, shrinking of the transplanted fat may occur and require additional procedures.

Retinitis pigmentosa.

Hereditary degenerations of the human retina are genetically heterogeneous, with well over 100 genes implicated so far. This Seminar focuses on the subset of diseases called retinitis pigmentosa, in which patients typically lose night vision in adolescence, side vision in young adulthood, and central vision in later life because of progressive loss of rod and cone photoreceptor cells. Measures of retinal function, such as the electroretinogram, show that photoreceptor function is diminished generally many years before symptomic night blindness, visual-field scotomas, or decreased visual acuity arise. More than 45 genes for retinitis pigmentosa have been identified. These genes account for only about 60% of all patients; the remainder have defects in as yet unidentified genes. Findings of controlled trials indicate that nutritional interventions, including vitamin A palmitate and omega-3-rich fish, slow progression of disease in many patients. Imminent treatments for retinitis pigmentosa are greatly anticipated, especially for genetically defined subsets of patients, because of newly identified genes, growing knowledge of affected biochemical pathways, and development of animal models.

Six patients with bradyopsia (slow vision): clinical features and course of the disease.

OBJECTIVE: Recently, it was discovered that subjects who showed a prolonged response suppression on their electroretinogram (ERG) and had symptoms of photophobia, problems adjusting to bright light, and difficulties seeing moving objects shared a mutation in the RGS9 (regulator of G-protein signaling 9) gene that is involved in the deactivation of photoreceptor responses. The disorder was termed bradyopsia (slow vision). This paper reports the clinical presentation and long-term follow-up of 6 bradyopsia patients. DESIGN: Retrospective observational case series with a follow-up ranging from 6 to 30 years. PARTICIPANTS: Six patients with a homozygous mutation in the RGS9 gene. METHODS: Clinical symptoms and signs were compared between the subjects and between their visits over time. MAIN OUTCOME MEASURES: Symptoms, visual acuity (VA), ocular findings, visual fields, dark-adaptation tests, color tests, fluorescein angiography, and ERG findings. RESULTS: Data showed a consistency in the individual symptoms and ERG recordings, but an extreme variation in VA between visits. Beside some irregularities in the macula in some patients, no other related eye abnormalities were seen. The low-to-subnormal VA varied with background luminance and typically increased by 2 to 3 lines when pinholes were used. Dark-adaptation tests, color tests, and fluorescein angiography were normal. Visual field tests showed a minor diffuse sensitivity loss. No progressive changes were seen over time. CONCLUSIONS: No signs of progression were noted in the 6 bradyopsia patients. Photophobia, impaired movement perception, variable reduced VA that improved with the use of pinholes and ERG abnormalities were typical for the disease.