Novel point-of-care biomarkers of the dry anophthalmic socket syndrome: tear film osmolarity and matrix metalloproteinase 9 immunoassay.

PURPOSE: To compare tear film osmolarity (TFO) values and matrix metalloproteinase 9 (MMP-9) levels between anophthalmic sockets and healthy fellow eyes and to assess the use of the MMP-9 and TFO as objective biomarkers for the dry anophthalmic socket syndrome (DASS). METHODS: In this prospective single-center study, the anophthalmic sockets and healthy fellow eyes of 98 unilateral anophthalmic patients were assessed using the ocular surface disease index (OSDI) questionnaire, InflammaDry® MMP-9 point-of-care immunoassay, TFO with TearLab™ Osmolarity System, and clinical conjunctival inflammation. MMP-9 concentration and conjunctival inflammation were graded semi-quantitatively. Differences between anophthalmic sockets and the healthy fellow eyes for OSDI scores, MMP-9, TFO values, clinical conjunctival inflammation, and eyelid abnormalities as well as the correlation between these factors and demographic data were evaluated. RESULTS: Patients had significantly higher OSDI, MMP-9, and TFO values, as well as higher conjunctival inflammation on the anophthalmic side, compared to the healthy side (p ≤ 0.002, respectively). For anophthalmic sockets, there was a significant positive correlation between OSDI scores and TFO values (p = 0.007), between the grade of posterior blepharitis and TFO values (p = 0.026), and between the conjunctival inflammation and MMP-9 values (p < 0.001), as well as between MMP-9 levels and time since eye loss (p = 0.004). CONCLUSIONS: Measuring MMP-9 and TFO may be helpful tools as efficient, quantifiable biomarkers, disease course parameters, or predictors for treatment response in the clinical management of patients with DASS or future therapy studies. Ophthalmologists should consider the updated diagnosis criteria including TFO and the definition for DASS proposed in this study.

Health Literacy in Patients Wearing Prosthetic Eyes: A Prospective Cross-Sectional Study.

PURPOSE: To investigate general and electronic health literacy (HL) levels in prosthetic eye wearing patients, to define factors associated with reduced HL, and to identify a potential healthcare gap. METHODS: In this prospective cross-sectional study 148 prosthetic eye wearers were screened using the 16-item European Health Literacy Survey Questionnaire (HLS-EU-Q16) and the 8-item electronic Health Literacy Scale (eHEALS). HLS-EU-16 and eHEALS scores were correlated to health levels, vision functioning, and sociodemographic factors. RESULTS: A total of 85 patients (57%) had adequate, 38 (26%) problematic, and 9 (6%) inadequate general HL, while 16 (11%) had no valid HLS-EU-Q16 score. General HL was positively correlated with physical health (p = 0.009) and negatively with a migration background (p = 0.023). There was a positive correlation between electronic HL and educational level (p < 0.001), social status (p = 0.048), and mental health (p = 0.013). Higher age was associated with lower electronic HL (p < 0.001). CONCLUSIONS: More than 30% of the prosthetic eye wearers had problematic or even inadequate general HL, suggesting a significant health care gap. To identify patients with reduced HL, a standardized screening tool should be implemented as part of routine clinical care. Within integrated care, patients with insufficient HL should be offered barrier-free advisory services and information brochures in various languages.

Post-enucleation socket syndrome-a novel pathophysiological definition.

BACKGROUND: The last definition of the post-enucleation socket syndrome (PESS) by Tyers and Collin-formulated almost 40 years ago in 1982-is predominantly based on the clinical characteristics and does not include the insights of newer studies into the pathophysiological mechanism of the PESS. METHODS: A systematic PubMed literature review regarding the pathophysiological mechanism of the PESS was performed, and results were comprised to give an overview of the current knowledge of the PESS including the exact pathophysiological mechanism. RESULTS: The primarily postulated pathophysiological mechanism of the PESS was the atrophy of orbital tissues, especially of fat, resulting in variable clinical findings. Newer studies using high-resolution computed tomography and magnetic resonance imaging or performing histopathological analyses found no orbital fat atrophy but rather a rotatory displacement of the orbital tissues from superior to posterior and from posterior to inferior together with the retraction of the extraocular muscles and a possible volume loss of the orbital implant by resorption if it is manufactured from hydroxyapatite. PESS results in a backward tilt of the superior fornix, a deep superior sulcus, a pseudo-ptosis, a lower eyelid elongation and laxity, a shallower inferior fornix, as well as enophthalmos and may lead to an inability of wearing ocular prostheses. CONCLUSIONS: A novel and comprehensive definition of the PESS is proposed: PESS is a multifactorial and variable syndrome caused by a rotatory displacement of orbital contents together with the retraction of the extraocular muscles and possible resorption of the orbital implant if it is manufactured from hydroxyapatite.

Towards improving the biocompatibility of prosthetic eyes.

Prosthetic eyes are currently manufactured using Poly(methyl methacrylate) (PMMA) which is not an ideal material because it is hydrophobic. While significant research has investigated the benefits of hydrophilic materials for contact lenses, no such research has been carried out on hydrophilic materials for prosthetic eyes until now. In this study, different derivatives of Poly(ethylene glycol) (PEG) monomer and methyl methacrylate (MMA) monomer were grafted to PMMA using copolymerisation. The resulting matrixes were evaluated by water contact angle measurement, 24 h water absorption testing, and colour-difference measurement when exposed to ultraviolet light. The contact angle and water absorption results indicated that ethylene glycol dimethacrylate (EGDMA) grafted PMMA matrix had a better hydrophilic performance than the other matrixes tested. EGDMA is already a minor constituent of the PMMA matrix currently used for manufacturing prosthetic eyes but when the proportion of EGDMA monomer to MMA monomer used in the manufacturing process was increased to 50/50 the hydrophilicity of the matrix was significantly improved. EGDMA-grafted PMMA is inexpensive and comes as a liquid monomer that is easily mixed with the PMMA monomer that ocular prosthetists are familiar with. The mixture requires no special handling beyond the normal safety precautions that apply when using PMMA monomers. In-vitro testing shows that EGDMA-grafted PMMA significantly improves the wettability of PMMA currently used for the manufacture of prosthetic eyes and has the potential to significantly improve wearing comfort and socket health.

Dry anophthalmic socket syndrome - morphological alterations in meibomian glands.

PURPOSE: To evaluate morphological alterations of meibomian glands (MGs) in the dry anophthalmic socket syndrome (DASS). METHODS: Fifteen unilateral anophthalmic patients wearing cryolite glass prosthetic eyes were enrolled. All patients with clinical blepharitis or other significant eyelid abnormalities were excluded. In vivo laser scanning confocal microscopy (LSCM) of the MGs in the lower eyelids both on the anophthalmic side and the healthy fellow eye was performed to quantify acinar unit density, acinar unit diameter, acinar unit area, meibum secretion reflectivity, the inhomogeneous appearance of the glandular interstice, and inhomogeneous appearance of the acinar walls. RESULTS: The lower eyelids of the anophthalmic sockets revealed a significant reduction of the acinar unit density (p = 0.003) as well as a significantly more inhomogeneous appearance of the periglandular interstices (p = 0.018) and the acinar unit walls (p = 0.015) than the healthy fellow eyelid. However, there were no significant differences regarding the acinar unit diameter, acinar unit area, and meibum secretion reflectivity of the MGs on the anophthalmic side compared to the healthy fellow eyelid (p ≥ 0.05, respectively). CONCLUSIONS: The eyelids of anophthalmic sockets without clinical blepharitis demonstrate a reduced density of MG acinar units and a more inhomogeneous appearance of the periglandular interstices and the acinar unit walls. This can cause meibomian gland dysfunction contributing to DASS and suggests early treatment of these symptomatic patients, even in the clinical absence of any blepharitis signs.

Anxiety and depression in patients wearing prosthetic eyes.

PURPOSE: To investigate anxiety and depression levels in prosthetic eye-wearing patients using standardized psychometric instruments, to define factors associated with these psychological diseases, and to identify a potential healthcare gap. METHODS: A total of 295 prosthetic eye wearers were screened using the 7-item generalized anxiety disorder scale (GAD-7) and the 9-item patient health questionnaire (PHQ-9). Scores of GAD-7 and PHQ-9 were correlated with scores of general physical and mental health functioning, vision-related quality of life, appearance-related distress, appearance-related social function, and further biosocial factors. RESULTS: Five patients (2%) had a pre-diagnosed anxiety disorder, and 20 patients (7%) had a pre-diagnosed depression. However, our screening revealed 26 patients (9%) with anxiety symptoms, 31 patients (11%) with depression symptoms, and 40 patients (14%) suffering from both anxiety and depression symptoms. This underdiagnosing for both anxiety and depression disorders was significant (p < 0.001, respectively). Higher GAD-7 scores were significantly associated with higher PHQ-9 scores, lower appearance-related social function, lower mental health functioning, and female gender (p ≤ 0.021, respectively). Higher PHQ-9 scores were significantly associated with lower physical and mental health functioning, higher educational degree, and non-traumatic eye loss (p ≤ 0.038, respectively). CONCLUSIONS: Anxiety and depression disorders seem to be underdiagnosed in prosthetic eye wearers and to have higher incidence compared with the general population. Therefore, a psychometric screening should be routinely implemented in the clinical care. For a successful long-term rehabilitation, integrated care by a multidisciplinary team including ophthalmic plastic surgeons, ophthalmologists, ocularists, general practitioners, and psychologists is essential.

Concerns regarding Indian prosthetic eye wearers.

CLINICAL RELEVANCE: Loss of an eye has a negative impact on the psychological health of a person. BACKGROUND: The aims are to: (a) identify the concerns of experienced prosthetic eye wearers in representative areas of India; (b) investigate how they change over time; (c) study how some demographic characteristics influence concerns; and (d) compare prosthetic eye concerns in India versus Germany and New Zealand. METHODS: This observational multi-centre study was conducted in the cities of Mumbai, Bengaluru and Delhi. Subjects aged from 18 to 65-years, with experience of at least two years of wearing a prosthetic eye fabricated from polymethyl methacrylate material, completed a validated questionnaire over the telephone. The questionnaire captured demographic data and general and prosthetic eye concerns at the time of eye loss and at the present time. RESULTS: At the time of eye loss, the five main concerns of participants were: health of the remaining eye; change in appearance; comfort; colour of the prosthesis; and movement of the prosthesis. However, after at least two years these concerns were significantly reduced (p < 0.05). The main present-day concern was watering, crusting and discharge, which was experienced by 81.1-per cent of the participants, 55.5-per cent of them on a daily basis. Compared with other demographic groups, blue-collar workers had higher odds of being concerned about the health of the remaining eye and least odds about prosthesis motility. Homemakers had higher odds of being concerned about wearing comfort and students had higher odds of being concerned about wearing comfort, appearance and health of the remaining eye. CONCLUSION: Initial concerns significantly reduce after two years. Watering, crusting and discharge are the most important current concerns for anophthalmic participants.

Depression, Anxiety and Stress Indicators for Prosthetic Eye Wearers.

BACKGROUND: This study explores the role of appearance, mucoid discharge, visual perception and functional problems as indicators for depression, anxiety and stress amongst prosthetic eye wearers. METHODS: A total of 217 anophthalmic patients who had worn a prosthetic eye for at least two years and were older than 16 years completed an anonymous questionnaire. Descriptive and inferential statistics were used to investigate differences and correlations between variables. RESULTS: The mean scores for depression, anxiety, and stress fell within the accepted normal ranges; however, 11% of participants experienced moderate depression, while 7% experienced severe or extremely severe levels. Ten percent were moderately anxious, and 7% were severely or extremely severely anxious. Five percent of participants were moderately stressed, while 7% were severely or extremely severely stressed. CONCLUSION: Social settings are important predictors for depression, whereas anxiety and stress appear to derive more from appearance concerns and practical issues. Prosthetic eye wearers with employment, leisure and social functioning issues are at higher risk of depression, anxiety and stress, as well as appearance, anxiety and not feeling accepted by society. Older patients and those who feel accepted by society appear to suffer less anxiety and stress. It is recommended that psychologists be a part of an integrated team to address the needs of anophthalmic patients.

Dry anophthalmic socket syndrome - Standardized clinical evaluation of symptoms and signs.

OBJECTIVES: To assess symptoms and signs of the dry anophthalmic socket syndrome (DASS) in a standardized manner. METHODS: 87 unilateral anophthalmic patients were evaluated using the Ocular Surface Disease Index (OSDI), the 5-Item Dry Eye Questionnaire (DEQ-5), and a modified version of Symptom Assessment iN Dry Eye (SANDE) questionnaire separately for the anophthalmic socket and for the healthy fellow eye. Conjunctival inflammation was semi-quantitatively graded and Schirmer I test with topical anesthesia was performed bilaterally. The correlations between scores of the dry eye questionnaires and the results of the Schirmer tests, conjunctival inflammation, and demographic data were examined. RESULTS: Patients had significantly higher OSDI, DEQ-5 and SANDE scores at the anophthalmic side compared to the healthy eye (p ≤ 0.019, respectively). 63% of patients complained of anophthalmic socket dryness in at least one of the three questionnaires. Patients had higher inflammation (p < 0.001) and more tear volume in the Schirmer I test with topical anesthesia (p ≤ 0.024) on the anophthalmic side compared to the fellow eye. CONCLUSIONS: Most anophthalmic patients have significantly more subjective dryness complaints on their anophthalmic side compared to the healthy fellow eye, even in absence of tear deficiency and clinical blepharitis. Eye care practitioners should consider the diagnosis criteria and the definition for DASS proposed in this study, when counseling anophthalmic patients. However, research should be undertaken to investigate the role and the interactions of causative etiological causes for DASS. Furthermore, there is a high priority to establish a standardized examination protocol and to develop an evidence-based treatment algorithm for DASS.

Cryolite glass prosthetic eyes-the response of the anophthalmic socket.

PURPOSE: To investigate mucoid discharge and the inflammatory response of anophthalmic sockets to cryolite glass prosthetic eye wear. PATIENTS AND METHODS: A total of 101 cryolite glass prosthetic eye wearers used visual analog scales (0-10) to measure frequency, color, volume, and viscosity of mucoid discharge associated with their prosthesis. Standardized photographs of the conjunctiva of their anophthalmic sockets were taken and conjunctival inflammation was semi-quantitatively graded (0-4). All characteristics of discharge and conjunctival inflammation were correlated to eye loss cause, hand washing behavior, and cleaning regimes as explanatory variables. RESULTS: Mean mucoid discharge characteristics (0-10 scale) were frequency 5.3 ± 2.8, color 4.8 ± 3.2, volume 4.9 ± 3.0, and viscosity 5.1 ± 3.2. The mean conjunctival inflammation score (0-4 scale) was 2.1 ± 1.0. There was a positive correlation between the grade of conjunctival inflammation and the frequency (p = 0.018), color (p = 0.001), volume (p = 0.003), and the viscosity of mucoid discharge (p = 0.005). More conjunctival inflammation was associated with higher frequency of cleaning (p < 0.001) and lower frequency of hand washing before removal (p = 0.001). Higher frequency, color, volume, and viscosity of discharge were associated with higher frequency of cleaning (p ≤ 0.001). CONCLUSIONS: Discharge severity associated with prosthetic eye wear was positively correlated with more conjunctival inflammation, higher cleaning frequency, and less hand washing before handling. The results suggest that cryolite glass eyes should not be removed daily for cleaning and that further research should be undertaken to develop a standardized treatment protocol for managing inflammation and mucoid discharge. This protocol would advise hand washing before handling cryolite glass eyes and recommend a minimum period of wear between cleaning sessions.

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.

Concerns of Anophthalmic Patients Wearing Cryolite Glass Prosthetic Eyes.

PURPOSE: To identify the main concerns of patients experienced in wearing cryolite glass prosthetic eyes and to investigate how these have changed over time. METHODS: One hundred six patients experienced in wearing prosthetic eyes for at least 2 years were asked to complete an anonymous questionnaire regarding prosthetic eye concerns at the time of initial eye loss and at the present time. Main outcome measures included changes in levels of concern over time. RESULTS: Initially, the participants were mainly concerned about their appearance, health of the fellow eye, and coping with monocularity. Over time, there was a significant increase of the level of concern regarding the health of the remaining eye (p < 0.001) and regarding watering, crusting, and discharge (p < 0.001). Loss of balance did not change significantly (p = 0.302). All other concerns decreased significantly over time (p < 0.001), with levels of concern about appearance decreasing the most. The current leading concern was the health of the remaining eye followed by concerns about watering, crusting, and discharge. Length of time since natural eye loss was the most important explanatory variable, with significant impact on the concerns about appearance (p = 0.013), retention of the prosthetic eye (p = 0.002), and eyelid contour (p = 0.004). CONCLUSIONS: Health of the remaining eye is the most common current concern of anophthalmic patients, acknowledging the need of good ophthalmologic follow up after losing an eye. The second most important concern is with watering, crusting, and discharge, suggesting further research for establishing an evidence-based protocol for cryolite glass prosthetic eye maintenance and supportive treatment.

An investigation into discharge, visual perception, and appearance concerns of prosthetic eye wearers.

We investigate prosthetic eye wearers' initial and current concerns about mucoid discharge, visual perception, and appearance, and the reasons for their concerns. A retrospective, cross-sectional study of private practice patients was designed. Participants were 217 experienced prosthetic eye wearers, aged at least 16 years. An anonymous questionnaire was e-mailed or mailed to participants. Descriptive and inferential statistics were used to investigate differences or correlations between variables. Content analysis was used to analyze participants' open responses. Participants were equally concerned about discharge, visual perception, and appearance during the first three months following eye loss and at least 2 years later, even though their concerns decreased. Older participants were less concerned about appearance, while females were more concerned about current discharge and appearance. The greater the frequency and volume of discharge, the greater was the concern. Participants' initial discharge concern was due to a negative interpretation of what it meant, but later, it was due to discomfort from wiping, and how discharge looked to others. Loss of depth perception and reduced visual range were equally concerning. Initial appearance concerns related to disguisability of the prosthesis, but over time, changes to the socket and eyelids became more important. Loss of self-image is commonly considered to be the major concern of anophthalmic patients, but discharge and visual perception concerns are of equal importance. Reasons given for these concerns provide greater insight into patients' personal experience of eye loss.

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.

Biosocial profile of New Zealand prosthetic eye wearers.

AIM: To describe the biosocial profile of New Zealand (NZ) artificial eye wearers and establish a basis for future research and international comparison. METHODS: This retrospective study surveyed 431 NZ artificial eye wearers to investigate their ethnicity, gender, age, causes of eye loss, age of current prosthesis, ocular prosthetic maintenance regimes and the extent and severity of discharge associated with prosthesis wear. RESULTS: Approximately 3000 people wear artificial eyes in NZ. Accidents were the main cause of eye loss prior to 1990 and medical conditions have been the main cause since. In the 1960s, the ratio of men to women losing an eye from accidents was 5:1, but during the past decade the ratio was 1.4:1. Socket discharge occurred at least twice daily for one-third of the study group. CONCLUSIONS: Approximately 1 in 1440 people wear artificial eyes in NZ. Decline of eye loss due to accidents is consistent with decreasing workplace and traffic accidents and may be due to improved medical management, workplace safety standards and safer roads. Mucoid discharge is prevalent in the anophthalmic population of NZ and an evidence based treatment protocol for discharge associated with prosthesis wear is needed. Research into this distressing condition is planned.