Clinical spectrum of non-syndromic microphthalmos, anophthalmos and coloboma in the paediatric population: a multicentric study from North India.

AIMS: To describe the clinical features, visual acuity and causes of ocular morbidity in children (0-18 years) with microphthalmos, anophthalmos, and coloboma (MAC) from North India. METHODS: A retrospective study conducted between October 2017 and September 2018 in three tertiary eye institutes, part of the Bodhya Eye Consortium with consensus led common pro formas. Children with complete clinical data and without syndromic/systemic involvement were included. The clinical phenotype was divided into isolated ocular coloboma (CB), coloboma with microcornea (CBMC), colobomatous microphthalmos (CBMO), non-colobomatous microphthalmos (MO) and anophthalmos (AO). RESULTS: A total of 532 children with MAC were examined. Seventeen records were excluded due to incomplete data (0.2%). 515 children (845 eyes) were included: 54.4% males and 45.6% females. MAC was unilateral in 36% and bilateral in 64%. CB, CBMC, CBMO, MO and AO were seen in 26.4%, 31%, 22%, 8% and 12.5% of eyes, respectively. Nystagmus was found in 40%, strabismus in 23%, cataract in 18.7% and retinal detachment in 15%. Best-corrected visual acuity (BCVA) of <3/60 was seen in 62.4% eyes. Blindness (BCVA <3/60 in better eye) was seen in 42.8% of bilateral patients. Those with microcornea or microphthalmos with coloboma had worse BCVA (p<0.001). There were regional differences in the type of MAC phenotype presenting to the three institutes. CONCLUSION: The MAC group of disorders cause significant ocular morbidity. The presence of microcornea or microphthalmos with coloboma predicts worse BCVA. The variation of the MAC phenotype with the district of origin of the patient raises questions of aetiology and is subject to further studies.

Visual function and quality of life in children and adolescents with anophthalmia and microphthalmia treated with ocular prosthesis.

PURPOSE: To evaluate health-related quality of life (HR-QoL), vision-related (VR-)QoL and perceptual visual dysfunction (PVD) among individuals with anophthalmia (A) and microphthalmia (M) treated with ocular prosthesis. METHODS: The study comprised 15 individuals (mean age 6.6 years; range 1.7-14.1) with unilateral A or M. Three validated instruments measuring HR-QoL and VR-QoL were used: The Pediatric QoL Inventory (PedsQL), consisting of physical and psychosocial self-report and parent-proxy report (2-18 years); Children's Visual Function Questionnaire (CVFQ); and Effects of Youngsters' Eyesight on Quality of Life (EYE-Q). Perceptual visual dysfunctions (PVDs) were assessed by history taking according to a specific protocol. RESULTS: A/M children and their parents showed low HR-QoL scores (PedsQL total score: 66.3; 69.6) compared with controls (83.0; 87.61) (p = 0.0035 and <0.0001, respectively, unpaired t-test). No differences were found between A/M children and parents, but parents tended to underestimate their children's emotional state. A/M children with subnormal visual acuity (VA) for age scored lower in physical health compared with A/M children with normal VA (p = 0.03, Mann-Whitney U-test). No significant VR-QoL differences between A/M children and references or between A/M children with subnormal or normal VA for age were found. More A/M children than controls exhibited PVDs in ≥1 area (7/11 versus 4/118; p < 0.0001, Fisher's exact test). CONCLUSION: A/M individuals show poor HR-QoL and increased PVDs. No difference in QoL was found between children and parents, though the children tended to score lower in emotional well-being. A/M children with subnormal VA showed lower physical health score. These problems indicate the necessity of a thorough multidisciplinary assessment and follow-up of children with A/M.

Eye Socket Regeneration and Reconstruction.

Purpose: When an eye has become irreversibly blind or painful it is removed by enucleation or evisceration. The resulting anophthalmic socket usually receives a volume replacing implant and is subsequently fitted with a prosthetic shell for adequate cosmesis. Trauma, tumour or immunological pathomechanisms can induce loss of bone, orbital soft tissue volume, and conjunctival contraction or implant exposure, which result in difficult or impossible prosthesis wear. In this situation as well as in numerous diseases limited to the conjunctiva (e.g. Pterygium, or cicatrizing conjunctivitis) strategies to substitute the lost tissue are required.Methods: A review of the literature search using various electronic databases (PubMed and MEDLINE) was performed on indications, surgical techniques and materials used to restore the ocular socket.Results: Amniotic membrane and oral mucosa are still the most commonly used substitutes for the reconstruction of larger conjunctival defects and ocular socket reconstruction. However, due to limitations of clinical available grafts, synthetic scaffolds, biomaterials or tissue-engineered grafts have been described in preclinical studies but most of them have not been investigated adequately in clinical studies yet. In orbital volume replacement, porous and nonporous spheres are used and both show acceptable results. However, more clinical studies are required that directly compare the outcomes in patients with similar conditions. Dermofat graft remains a good option in case of sockets with significant orbital volume and conjunctival surface loss.Conclusion: Beyond established techniques using autologous or allogeneic tissue, various approaches of engineering tissue based on scaffolds and stem cell expansion techniques are currently under investigation and may become alternatives in socket reconstruction in the not too far future.

Structural and functional brain reorganisation due to blindness: The special case of bilateral congenital anophthalmia.

Investigating the changes in the brain that result from a loss of sensory input has provided significant insight into the considerable capacity of the brain to reorganise. One of the difficulties in studying sensory-deprived populations is that the time and extent of sensory loss vary significantly. In this review, we consider the changes in the human brain associated with complete absence of visual input resulting from bilateral congenital anophthalmia, in which the eyes fail to develop. We describe the functional reorganisation and associated structural and connectivity changes that occur in the brain of those affected by the condition. By considering animal models of this condition, we investigate the changes that may be occurring on a scale that is not captured by human in vivo imaging techniques. Finally, we lay out a model pathway for taking auditory information to the occipital cortex that may be specific to anophthalmia.

Growth and Behavior of Congenitally Anophthalmic Lee-Sung Pigs.

Circadian rhythm is usually regulated by the environmental light-dark cycle. Congenitally anophthalmic miniature pigs provide a valuable model for the study of factors affecting circadian rhythms in the absence of visual exposure to the light-dark cycle. This study investigated the growth and daily behavior patterns of Lee-Sung pigs with congenital anophthalmia. Growth in 5 Lee-Sung pigs (LSP) with congenital anophthalmia (LSP-A) and 10 normally developed pigs (LSP-N) was assessed when they were 1 through 6 mo old. Behavioral studies using digital video recording were completed in 6 sexually mature LSP (3 LSP-A and 3 LSP-N). MRI showed that LSP-A lose their vision because of a lack of retinal input and optic chiasm development. LSP-N and LSP-A did not differ in body weight or size at 2, 4, and 6 mo of age. Behavior and activity pattern studies showed that both LSP-A and LSP-N were active mainly during daylight, but LSP-A spent significantly more time exploring their environment during the day (28%) and night (10%) than did LSP-N. This study revealed that growth performance was similar between LSP-A and normal pigs, but their behavior and activity patterns differed. LSP-A showed circadian rhythm abnormalities similar to those in blind humans. This study provides basic data on LSP-A as a model for studying compensatory cross-modal brain plasticity and hormone regulation in the absence of retinal input is deficient and for understanding the role of circadian rhythm regulation.

Early Blindness Shapes Cortical Representations of Auditory Frequency within Auditory Cortex.

Early loss of vision is classically linked to large-scale cross-modal plasticity within occipital cortex. Much less is known about the effects of early blindness on auditory cortex. Here, we examine the effects of early blindness on the cortical representation of auditory frequency within human primary and secondary auditory areas using fMRI. We observe that 4 individuals with early blindness (2 females), and a group of 5 individuals with anophthalmia (1 female), a condition in which both eyes fail to develop, have lower response amplitudes and narrower voxelwise tuning bandwidths compared with a group of typically sighted individuals. These results provide some of the first evidence in human participants for compensatory plasticity within nondeprived sensory areas as a result of sensory loss.SIGNIFICANCE STATEMENT Early blindness has been linked to enhanced perception of the auditory world, including auditory localization and pitch perception. Here we used fMRI to compare neural responses with auditory stimuli within auditory cortex across sighted, early blind, and anophthalmic individuals, in whom both eyes fail to develop. We find more refined frequency tuning in blind subjects, providing some of the first evidence in human subjects for compensation within nondeprived primary sensory areas as a result of blindness early in life.

Congenital Bilateral Anophthalmia: a Case Report and Review of Literature.

INTRODUCTION: Anophthalmia is congenital absence of the eyes; it may be unilateral or bilateral. Though rare, it occurs worldwide. It usually occurs in association with other systemic malformations. CASE REPORT: Therefore, the case of a female child delivered in University Clinic Center Tuzla is presented here with bilateral anophthalmia. The diagnosis was confirmed with an ocular computer tomography (CT) scan that showed under development of both globes within the orbit with a conclusion of bilateral anophthalmia. No other anomalies were found. CONCLUSION: This is unique case in the territory of Bosnia and Herzegovina, as according to the literature this is the first case of anophthalmia presented in this region. Currently two years ago she is followed both in ophthalmic and pediatric clinic at University Clinical Center in Tuzla.

A novel deletion mutation of the SOX2 gene in a child of Chinese origin with congenital bilateral anophthalmia and sensorineural hearing loss.

Congenital anophthalmia is a rare eye anomaly which lacks a recognizable eye in the orbit. It can be isolated (nonsyndromic) or be observed as a sign of other diseases (syndromic). A Chinese infant was born with bilateral anophthalmia and palpebral fissure closures. Ocular and systemic examinations were performed, and genomic DNA was prepared from peripheral leukocytes. The coding exons and the adjacent intrinsic sequence of SOX2 were analysed by Sanger sequencing. A c.70_89del (p. Asn24ArgfsX65; rs398123693) mutation in SOX2 was identified in the Chinese infant with bilateral clinical anophthalmia and sensorineural hearing loss. Thismutation was not detected in the unaffected parents and 150 unaffected control individuals.Mutation in SOX2 is associated with bilateral clinical anophthalmia and probablywith other anomalies in the Chinese infant. Until nowhearing loss has not been reported in individuals with SOX2 mutation. The results remind us that clinical anophthalmia may be accompanied by sensorineural hearing loss and may be associated with SOX2 mutation, and it will contribute to improving diagnosis and patient care. Given that children with anophthalmia already have reduced sight, it seems worthwhile to make a point of careful vigilance on hearing for all such patients.

Functional vision and quality of life in children with microphthalmia/anophthalmia/coloboma-a cross-sectional study.

PURPOSE: To determine the child's and parental perception of functional visual ability (FVA), vision-related and health-related quality of life (VR-QoL, HR-QoL) in children with microphthalmia/anophthalmia/coloboma (MAC). METHODS: Between June 25, 2014, and June 3, 2015, we carried out a cross-sectional observational study at Moorfields Eye Hospital, London, UK, enrolling 45 children 2-16 years of age with MAC attending our clinics, and their parents. To assess FVA, VR-QoL, and HR-QoL we asked participants to complete three validated tools, the Cardiff Visual Ability Questionnaire for Children (CVAQC), the Impact of Vision Impairment for Children (IVI-C) instrument, and the PedsQL V 4.0. The main outcome measures were the FVA, VR-QoL, and HR-QoL scores, reported by children and parents. RESULTS: In children with MAC, FVA is moderately reduced, with a median CVAQC score of -1.4 (IQR, -2.4 to 0.4; range, -3.0 [higher FVA] to +2.8 [lower FVA]). VR-QoL and HR-QoL are greatly reduced, with an IVI-C median score of 63 (IQR, 52-66; normal VR-QoL, 96), a median self-reported PedsQL score of 77 (IQR, 71-90; normal HR-QoL, 100) and parental score of 79 (IQR, 61-93), and a family impact score of 81 (67-93). Psychosocial well-being scores are lower than physical well-being scores. Parents and children have a different perception of the impact of the condition on the child's HR-QoL. CONCLUSIONS: MAC has a significant impact on a child's FVA and QoL, similar to that described by children with acute lymphoblastic leukaemia and chronic systemic conditions. Children and families may benefit from psychosocial support.

Concerns of anophthalmic patients-a comparison between cryolite glass and polymethyl methacrylate prosthetic eye wearers.

PURPOSE: To compare the concerns of experienced cryolite glass and (poly)methyl methacrylate (PMMA) prosthetic eye wearers. METHODS: One hundred six experienced cryolite glass and 63 experienced PMMA prosthetic eye wearers completed an anonymous questionnaire regarding general and specific prosthetic eye concerns at least 2 years after natural eye loss. From these independent anophthalmic populations, we identified 34 case-control pairs matched for the known influencing demographic variables of gender, occupation, age, and time since natural eye loss. RESULTS: The levels of concern were significantly lower in the cryolite glass group than those in the PMMA group for the following: loss of balance (p < 0.001), phantom sight vision (p < 0.001), pain (p < 0.001), receiving good advice (p = 0.001), fullness of orbit (p = 0.001), size (p = 0.007), direction of gaze relative to the healthy fellow eye (p = 0.005), eye lid contour (p = 0.037), comfort of the prosthetic eye (p < 0.001), colour relative to the healthy fellow eye (p < 0.001), and retention of the prosthetic eye (p < 0.001). Concerns about watering, crusting, discharge, visual perception, appearance, movement of the prosthetic eye, and health of the remaining eye were not significantly different between both groups. CONCLUSIONS: The results of this study showed that many general and specific levels of concern were significantly lower for cryolite glass prosthetic eye wearers than for PMMA prosthetic eye wearers. The question of why there are significant differences and to what extent the material of the prosthesis (cryolite glass or PMMA) has an impact on various concerns remains unanswered and should be addressed in a prospective comparative multicentre trial.

Congenital Anophthalmia and Binocular Neonatal Enucleation Differently Affect the Proteome of Primary and Secondary Visual Cortices in Mice.

In blind individuals, visually deprived occipital areas are activated by non-visual stimuli. The extent of this cross-modal activation depends on the age at onset of blindness. Cross-modal inputs have access to several anatomical pathways to reactivate deprived visual areas. Ectopic cross-modal subcortical connections have been shown in anophthalmic animals but not in animals deprived of sight at a later age. Direct and indirect cross-modal cortical connections toward visual areas could also be involved, yet the number of neurons implicated is similar between blind mice and sighted controls. Changes at the axon terminal, dendritic spine or synaptic level are therefore expected upon loss of visual inputs. Here, the proteome of V1, V2M and V2L from P0-enucleated, anophthalmic and sighted mice, sharing a common genetic background (C57BL/6J x ZRDCT/An), was investigated by 2-D DIGE and Western analyses to identify molecular adaptations to enucleation and/or anophthalmia. Few proteins were differentially expressed in enucleated or anophthalmic mice in comparison to sighted mice. The loss of sight affected three pathways: metabolism, synaptic transmission and morphogenesis. Most changes were detected in V1, followed by V2M. Overall, cross-modal adaptations could be promoted in both models of early blindness but not through the exact same molecular strategy. A lower metabolic activity observed in visual areas of blind mice suggests that even if cross-modal inputs reactivate visual areas, they could remain suboptimally processed.

Resting-State Retinotopic Organization in the Absence of Retinal Input and Visual Experience.

Early visual areas have neuronal receptive fields that form a sampling mosaic of visual space, resulting in a series of retinotopic maps in which the same region of space is represented in multiple visual areas. It is not clear to what extent the development and maintenance of this retinotopic organization in humans depend on retinal waves and/or visual experience. We examined the corticocortical receptive field organization of resting-state BOLD data in normally sighted, early blind, and anophthalmic (in which both eyes fail to develop) individuals and found that resting-state correlations between V1 and V2/V3 were retinotopically organized for all subject groups. These results show that the gross retinotopic pattern of resting-state connectivity across V1-V3 requires neither retinal waves nor visual experience to develop and persist into adulthood. Significance statement: Evidence from resting-state BOLD data suggests that the connections between early visual areas develop and are maintained even in the absence of retinal waves and visual experience.

Anoftalmo congénito familiar / Congenital Anophthalmus

Se presentan las características oftalmológicas de tres pacientes, dos hermanos: una hembra, un varón y su madre con diagnóstico de anoftalmo congénito. El anoftalmo es un trastorno genético que se produce cuando hay fallo en el desarrollo del neuroectodermo a partir de la placa neural anterior del tubo neural, durante el desarrollo embriológico, esta anomalía aparece intrautero, por lo que es congénita, puede ser unilateral o bilateral, de etiología idiopática, esporádica. Se presenta por una herencia recesiva o ligada al sexo: trisomia 13–15. Estos pacientes se caracterizan por la ausencia del globo ocular en la cavidad orbitaria, orbitas pequeñas, con reducción de la cavidad ósea, agujeros ópticos pequeños, musculatura extrínseca ausente así como las glándulas y conductos lagrimales, hay acortamiento de los párpados, marcada disminución de los fondos sacos, con fornix conjuntival poco profundos, con particulares casi idénticas en los tres pacientes, la diferencia es que el hermano varón y la madre presentan anoftalmo unilateral y la hermana anoftalmo bilateral(AU)

There are discussed the ophthalmologic characteristics of three patients, two siblings (male and female) and their mother with diagnosis of congenital anophthalmus. The anophthalmus is a genetic disorder that is produced when there is a failure in the neuroectoderm development starting from the anterior neural plate to the neural tube, during the embryologic development; this is a unilateral intrauterine anomaly, for which it is congenital, and may be unilateral or bilateral with idiopathic and sporadic etiology. It is presented by a recessive or bound inheritance to the sex: trisomy 13-15. These patients are characterized by the absence of the eyeball in the orbital cavity, small orbits, with reduction of the bone cavity, small optic holes, absent extrinsic musculature as well as the glands and lachrymal conduits. There is a reduction of the eyelids, a marked decrease of the sacs, with shallow fornix conjunctivae, almost identical features in the three patients; the difference is that the male and his mother have unilateral anophthalmus and the daughter has bilateral anophthalmus(EU)

Strain differences of the effect of enucleation and anophthalmia on the size and growth of sensory cortices in mice.

Anophthalmia is a condition in which the eye does not develop from the early embryonic period. Early blindness induces cross-modal plastic modifications in the brain such as auditory and haptic activations of the visual cortex and also leads to a greater solicitation of the somatosensory and auditory cortices. The visual cortex is activated by auditory stimuli in anophthalmic mice and activity is known to alter the growth pattern of the cerebral cortex. The size of the primary visual, auditory and somatosensory cortices and of the corresponding specific sensory thalamic nuclei were measured in intact and enucleated C57Bl/6J mice and in ZRDCT anophthalmic mice (ZRDCT/An) to evaluate the contribution of cross-modal activity on the growth of the cerebral cortex. In addition, the size of these structures were compared in intact, enucleated and anophthalmic fourth generation backcrossed hybrid C57Bl/6J×ZRDCT/An mice to parse out the effects of mouse strains and of the different visual deprivations. The visual cortex was smaller in the anophthalmic ZRDCT/An than in the intact and enucleated C57Bl/6J mice. Also the auditory cortex was larger and the somatosensory cortex smaller in the ZRDCT/An than in the intact and enucleated C57Bl/6J mice. The size differences of sensory cortices between the enucleated and anophthalmic mice were no longer present in the hybrid mice, showing specific genetic differences between C57Bl/6J and ZRDCT mice. The post natal size increase of the visual cortex was less in the enucleated than in the anophthalmic and intact hybrid mice. This suggests differences in the activity of the visual cortex between enucleated and anophthalmic mice and that early in-utero spontaneous neural activity in the visual system contributes to the shaping of functional properties of cortical networks.

A splice donor mutation in NAA10 results in the dysregulation of the retinoic acid signalling pathway and causes Lenz microphthalmia syndrome.

INTRODUCTION: Lenz microphthalmia syndrome (LMS) is a genetically heterogeneous X-linked disorder characterised by microphthalmia/anophthalmia, skeletal abnormalities, genitourinary malformations, and anomalies of the digits, ears, and teeth. Intellectual disability and seizure disorders are seen in about 60% of affected males. To date, no gene has been identified for LMS in the microphthalmia syndrome 1 locus (MCOPS1). In this study, we aim to find the disease-causing gene for this condition. METHODS AND RESULTS: Using exome sequencing in a family with three affected brothers, we identified a mutation in the intron 7 splice donor site (c.471+2T→A) of the N-acetyltransferase NAA10 gene. NAA10 has been previously shown to be mutated in patients with Ogden syndrome, which is clinically distinct from LMS. Linkage studies for this family mapped the disease locus to Xq27-Xq28, which was consistent with the locus of NAA10. The mutation co-segregated with the phenotype and cDNA analysis showed aberrant transcripts. Patient fibroblasts lacked expression of full length NAA10 protein and displayed cell proliferation defects. Expression array studies showed significant dysregulation of genes associated with genetic forms of anophthalmia such as BMP4, STRA6, and downstream targets of BCOR and the canonical WNT pathway. In particular, STRA6 is a retinol binding protein receptor that mediates cellular uptake of retinol/vitamin A and plays a major role in regulating the retinoic acid signalling pathway. A retinol uptake assay showed that retinol uptake was decreased in patient cells. CONCLUSIONS: We conclude that the NAA10 mutation is the cause of LMS in this family, likely through the dysregulation of the retinoic acid signalling pathway.

Early auditory processing in area V5/MT+ of the congenitally blind brain.

Previous imaging studies of congenital blindness have studied individuals with heterogeneous causes of blindness, which may influence the nature and extent of cross-modal plasticity. Here, we scanned a homogeneous group of blind people with bilateral congenital anophthalmia, a condition in which both eyes fail to develop, and, as a result, the visual pathway is not stimulated by either light or retinal waves. This model of congenital blindness presents an opportunity to investigate the effects of very early visual deafferentation on the functional organization of the brain. In anophthalmic animals, the occipital cortex receives direct subcortical auditory input. We hypothesized that this pattern of subcortical reorganization ought to result in a topographic mapping of auditory frequency information in the occipital cortex of anophthalmic people. Using functional MRI, we examined auditory-evoked activity to pure tones of high, medium, and low frequencies. Activity in the superior temporal cortex was significantly reduced in anophthalmic compared with sighted participants. In the occipital cortex, a region corresponding to the cytoarchitectural area V5/MT+ was activated in the anophthalmic participants but not in sighted controls. Whereas previous studies in the blind indicate that this cortical area is activated to auditory motion, our data show it is also active for trains of pure tone stimuli and in some anophthalmic participants shows a topographic mapping (tonotopy). Therefore, this region appears to be performing early sensory processing, possibly served by direct subcortical input from the pulvinar to V5/MT+.

Serial sub-conjunctival 5-Fluorouracil for early recurrent anophthalmic contracted socket.

BACKGROUND: To evaluate the effects and side-effects of serial sub-conjunctival injections of 5-fluorouracil (5-FU) in early postoperative period for recurrent anophthalmic contracted socket. METHODS: Retrospective comparative case series at tertiary eye care centre including fifteen adult patients with features of postoperative recurrent socket contraction after buccal mucosal graft. Group A comprised eight patients treated with 10 mg weekly sub-conjunctival injection of 5-FU in the fornices. Group B comprised seven patients taken as control. Main outcome measures were: superior fornix depth (SFD), inferior fornix depth (IFD), and socket volume (SV) at 6 months follow up. Patients were re-evaluated clinically for recurrence at last follow-up. RESULTS: The mean ± SD values in group A versus group B were as follows: 10 ± 1.6 mm vs 5.1 ± 0.9 mm (p < 0.005) for SFD, 6.7 ± 1.5 mm vs 3.5 ± 0.5 mm (p = 0.02) for IFD; and 2 ± 0.55 ml versus 0.27 ± 0.06 ml (p = 0.005) for SV at 6 months. There was significant improvement in depth of fornices and volume of socket in seven patients in group A. One patient in group A did not benefit from 5-FU treatment. The beneficial effects of 5-FU were observed when first injection was given within 4 weeks after socket reconstruction. There was no recurrence (in six cases) and no side-effects seen in group A at final follow-up of 18.2 (12-24) months. CONCLUSIONS: Weekly injections of 5-FU are effective for stopping the progression of recurrent contracted socket following primary reconstructive surgery. It provides early rehabilitation, and avoids repetitive surgery.

A proposed model of the response of the anophthalmic socket to prosthetic eye wear and its application to the management of mucoid discharge.

Mucoid discharge associated with prosthetic eye wear can be a distressing condition that affects the quality of life of people who have lost an eye. Discharge is the second highest concern of experienced prosthetic eye wearers after health of the companion eye and is prevalent in anophthalmic populations. Specific causes of mucoid discharge such as infections and environmental allergens are well understood, but non-specific causes are unknown and an evidence based protocol for managing non-specific discharge is lacking. Current management is based on prosthesis removal and cleaning, and professional re-polishing of the prosthesis. Tear protein deposits accumulate on prosthetic eyes. These deposits mediate the response of the socket to prosthetic eye wear and their influence (good and bad) is determined by differing cleaning regimes and standards of surface finish. This paper proposes a three-phase model that describes the response of the socket to prosthetic eye wear. The phases are: An initial period of wear of a new (or newly-polished) prosthesis when homeostasis is being established (or re-established) within the socket; a second period (equilibrium phase) where beneficial surface deposits have built up on the prosthesis and wear is safe and comfortable, and a third period (breakdown phase) where there is an increasing likelihood of harm from continued wear. The proposed model provides a rationale for a personal cleaning regime to manage non-specific mucoid discharge. Professional care of prosthetic eyes is also important for the management of discharge and evidence for effective surface finishing is reported in this study. Taken together, the proposed regimes for personal and professional care comprise a protocol for managing discharge associated with prosthetic eye wear. The protocol describes prosthetic eye cleaning methods and frequency, and suggests minimum standards for professional polishing. If confirmed, the protocol has the potential to resolve the current varied and contradictory opinions about the management of discharge, and to clarify advice given to patients about how to personally care for their prosthetic eyes.