Keratin films for ocular surface reconstruction: Wound healing in an in-vivo model.

The most commonly used tissue substitute for ocular surface reconstruction is human amniotic membrane (AM). Because of its low biomechanical strength and intransparency there is a need to search for alternatives of consistent quality. This study, further explored the biocompatibility of Keratin Film (KF) and its ability to sustain corneal epithelial wound healing. In three equal groups of 5 New Zeeland white rabbits a 4 mm superficial keratectomy was created in the right eye. Five eyes received a KF, five a human AM graft and the remaining five no implant. All eyes were treated with ofloxacin and dexamethasone eye drops and followed up for 10 days. Corneal fluorescein staining, vascularization, and transparency were assessed using slit lamp biomicroscopy according to a standardized grading score during and at the end of follow-up. The corneal-scleral-button was excised and processed for histology. After 10 days all eyes which had received a KF showed complete epithelial healing and no signs of neovascularization. In the AM group 1 eye showed a persistent epithelial defect at day 10 and 2 eyes showed neovascularization at day 7 resolving at day 10. Transparency improved progressively both in the KF group as well as in the AM group towards the end of the follow. Histology showed a multilayer epithelium firmly adherent to the KF with no evidence of keratocyte migration or inflammatory reaction in the corneal stroma. In this study on rabbit eyes KF better supported corneal epithelial wound healing than amniotic membrane.

Influence of short-term face mask wear on semiautomatically measured tear film parameters in dry eye patients and healthy volunteers.

PURPOSE: The use of face masks has been proposed to cause or exacerbate the symptoms of dry eye disease (DED), which has been widely discussed under the term mask-associated dry eye (MADE). However, no studies have systematically investigated tear film parameters during the use of different face masks. Therefore, the objective of the present study was to investigate clinically relevant parameters of the tear film before and during the short-time use of face masks in dry and normal eyes. METHODS: In a prospective study, the tear film parameters of 42 DED patients and 42 healthy volunteers were examined while wearing different types of face masks in a randomized order. This included measurements of non-invasive tear break-up time (NIBUT), lipid layer thickness, tear meniscus height, and bulbar redness after 30 min of wearing no mask, a surgical face mask or an FFP2/K95 mask. The equivalence of the means was assessed using the two one-sided t-test (TOST) method. RESULTS: In healthy volunteers' lipid layer thickness, NIBUT and tear meniscus height were not significantly altered by 30 min of surgical or FFP2 mask wear (p > 0.016). The use of either type of mask was significantly associated with decreased bulbar redness (p < 0.001) in healthy eyes. In patients with DED, none of the tear film parameters or bulbar redness were significantly altered by 30 min of mask wear (p > 0.016). CONCLUSIONS: Based on these results, the short-term wearing of face masks, regardless of type, did not produce a significant difference in tear film parameters of lipid layer thickness, NIBUT, and tear meniscus in healthy or dry eyes, while bulbar redness was reduced after mask wear only in healthy volunteers.

Rare periorbital, pseudocystic metastasis of squamous cell carcinoma of the bladder: Case report and review of the literature.

We present the case of a man in his fifties with a history of bladder carcinoma who presented with a large periorbital cystic lesion that was found to be a metastasis. Bladder carcinomas are a very rare cause of peri-/orbital metastasis. The primary tumor in this case predominately showed squamous cell differentiation and small areas of adenoid differentiation. To our knowledge only one previous case of orbital metastasis from squamous cell carcinoma of the bladder has been reported. Cyst formation in bladder cancer metastasis has not been reported and is very rare for orbital metastases in general. The pathogenesis of metastatic cyst development is not fully understood and may vary from case to case. A biopsy of an atypical cyst is indicated.

Automated vs. human evaluation of corneal staining.

BACKGROUND AND PURPOSE: Corneal fluorescein staining is one of the most important diagnostic tests in dry eye disease (DED). Nevertheless, the result of this examination is depending on the grader. So far, there is no method for an automated quantification of corneal staining commercially available. Aim of this study was to develop a software-assisted grading algorithm and to compare it with a group of human graders with variable clinical experience in patients with DED. METHODS: Fifty images of eyes stained with 2 µl of 2% fluorescein presenting different severity of superficial punctate keratopathy in patients with DED were taken under standardized conditions. An algorithm for detecting and counting superficial punctate keratitis was developed using ImageJ with a training dataset of 20 randomly picked images. Then, the test dataset of 30 images was analyzed (1) by the ImageJ algorithm and (2) by 22 graders, all ophthalmologists with different levels of experience. All graders evaluated the images using the Oxford grading scheme for corneal staining at baseline and after 6-8 weeks. Intrarater agreement was also evaluated by adding a mirrored version of all original images into the set of images during the 2nd grading. RESULTS: The count of particles detected by the algorithm correlated significantly (n = 30; p < 0.01) with the estimated true Oxford grade (Sr = 0,91). Overall human graders showed only moderate intrarater agreement (K = 0,426), while software-assisted grading was always the same (K = 1,0). Little difference was found between specialists and non-specialists in terms of intrarater agreement (K = 0,436 specialists; K = 0,417 non-specialists). The highest interrater agreement was seen with 75,6% in the most experienced grader, a cornea specialist with 29 years of experience, and the lowest was seen in a resident with 25,6% who had only 2 years of experience. CONCLUSION: The variance in human grading of corneal staining - if only small - is likely to have only little impact on clinical management and thus seems to be acceptable. While human graders give results sufficient for clinical application, software-assisted grading of corneal staining ensures higher consistency and thus is preferrable for re-evaluating patients, e.g., in clinical trials.

DMEK after penetrating keratoplasty: cohort with DMEK grafts and descemetorhexis larger than full-thickness graft.

PURPOSE: The study aims to evaluate visual outcome, central corneal thickness, and rebubbling rate in a cohort with oversized DMEK grafts after failed penetrating keratoplasty (PK). The unique feature of the study is a descemetorhexis diameter larger than the full-thickness graft, i.e., peripheral to the PK interface. METHODS: A monocentric, retrospective evaluation of all patients with endothelial graft failure after PK treated with an oversized DMEK graft and descemetorhexis outside of the PK interface (i.e., in host tissue) between January 2015 and July 2019 at the Department of Ophthalmology at the University of Düsseldorf (Germany) was performed. RESULTS: Eleven eyes of 10 patients were identified. Mean age was 69 years. On average (arithmetic mean ± standard deviation), 1.7 ± 1.0 previous PKs have been performed per eye in this cohort. The mean time between last PK and DMEK was 10.1 ± 7.3 years (range 2 to 23 years). In all cases, the graft diameter exceeded the diameter of the previous PK and descemetorhexis was performed in host tissue, that is, peripheral to the graft-host interface. Rebubbling was performed in 18.2% of the patients (n = 2 eyes) because of central graft detachment. Mean central corneal thickness showed a statistically significant improvement at 5.3 ± 3.5 months after surgery from 688.23 ± 151.01 to 527.75 ± 88 µm (p = 0.002). Visual acuity increased significantly by 5 lines from 1.24 ± 0.5 logMAR (range from 0.5 to 2) to 0.73 ± 0.76 logMAR (range from 0.1 to 2) within 3 months (p = 0.006). Excluding patients without visual potential and transplant failure, visual acuity improved significantly by 8 lines (p < 0.001), and stayed stable until the last follow-up at 15.1 ± 11.4 months (range 6 to 39 months, p < 0.001, n = 8) after surgery. CONCLUSION: DMEK can be successfully used to treat endothelial cell failure after PK, and can provide good postoperative results with regards to visual acuity. This study shows that stripping of Descemet's membrane (DM) peripheral to the PK interface is surgically feasible. Overlapping, larger DMEK grafts with more endothelial cells can be used without increasing rebubbling rates and may potentially improve long-term graft survival.

European Guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part II.

This guideline has been initiated by the task force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology, including physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline that systematically reviewed the literature on mucous membrane pemphigoid (MMP) in the MEDLINE and EMBASE databases until June 2019, with no limitations on language. While the first part of this guideline addressed methodology, as well as epidemiology, terminology, aetiology, clinical presentation and outcome measures in MMP, the second part presents the diagnostics and management of MMP. MMP should be suspected in cases with predominant mucosal lesions. Direct immunofluorescence microscopy to detect tissue-bound IgG, IgA and/or complement C3, combined with serological testing for circulating autoantibodies are recommended. In most patients, serum autoantibodies are present only in low levels and in variable proportions, depending on the clinical sites involved. Circulating autoantibodies are determined by indirect IF assays using tissue substrates, or ELISA using different recombinant forms of the target antigens or immunoblotting using different substrates. The major target antigen in MMP is type XVII collagen (BP180), although in 10-25% of patients laminin 332 is recognized. In 25-30% of MMP patients with anti-laminin 332 reactivity, malignancies have been associated. As first-line treatment of mild/moderate MMP, dapsone, methotrexate or tetracyclines and/or topical corticosteroids are recommended. For severe MMP, dapsone and oral or intravenous cyclophosphamide and/or oral corticosteroids are recommended as first-line regimens. Additional recommendations are given, tailored to treatment of single-site MMP such as oral, ocular, laryngeal, oesophageal and genital MMP, as well as the diagnosis of ocular MMP. Treatment recommendations are limited by the complete lack of high-quality randomized controlled trials.

European guidelines (S3) on diagnosis and management of mucous membrane pemphigoid, initiated by the European Academy of Dermatology and Venereology - Part I.

This guideline on mucous membrane pemphigoid (MMP) has been elaborated by the Task Force for Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology (EADV) with a contribution of physicians from all relevant disciplines and patient organizations. It is a S3 consensus-based guideline encompassing a systematic review of the literature until June 2019 in the MEDLINE and EMBASE databases. This first part covers methodology, the clinical definition of MMP, epidemiology, MMP subtypes, immunopathological characteristics, disease assessment and outcome scores. MMP describes a group of autoimmune skin and mucous membrane blistering diseases, characterized by a chronic course and by predominant involvement of the mucous membranes, such as the oral, ocular, nasal, nasopharyngeal, anogenital, laryngeal and oesophageal mucosa. MMP patients may present with mono- or multisite involvement. Patients' autoantibodies have been shown to be predominantly directed against BP180 (also called BPAG2, type XVII collagen), BP230, laminin 332 and type VII collagen, components of junctional adhesion complexes promoting epithelial stromal attachment in stratified epithelia. Various disease assessment scores are available, including the Mucous Membrane Pemphigoid Disease Area Index (MMPDAI), the Autoimmune Bullous Skin disorder Intensity Score (ABSIS), the 'Cicatrising Conjunctivitis Assessment Tool' and the Oral Disease Severity Score (ODSS). Patient-reported outcome measurements (PROMs), including DLQI, ABQOL and TABQOL, can be used for assessment of quality of life to evaluate the effectiveness of therapeutic interventions and monitor disease course.

[Significance of New Methods of Examining the Tear Film in Dry Eye Disease: Tear Film Osmolarity and Matrix Metalloproteinases (MMP-9)]. / Stellenwert neuer Untersuchungsmethoden des Tränenfilms in der Diagnostik des trockenen Auges: Tränenfilmosmolarität und Matrixmetalloproteinasen (MMP-9).

Dry eye disease is one of the most common diagnoses in ophthalmology. A variety of subjective and objective test methods with imprecise limits and highly different sensitivities and specificities complicate the diagnosis. Especially mild to moderate pathological findings can be misdiagnosed. In recent years, new options have opened, through the development of new, clinical practicable diagnostic equipment, for example, for the analysis of tear film osmolarity or matrix metalloproteinases (MMP-9). The value of tear film osmolarity and determination of MMP-9 levels in the diagnosis of dry eye and its subtypes will be discussed and evaluated objectively, on the basis of published study results.

[Keratoplasty in Children and Adolescents]. / Keratoplastiken im Kindes- und Jugendalter.

BACKGROUND: The conditions for long-term graft survival in infants and children are unfavorable, due to the different immunological features, the impaired clinical examination and the reduced compliance and treatment adherence. However, penetrating keratoplasty is often the only option to prevent amblyopia and there may be no alternative. We examined the different indications, graft survival and complications in two specialised centres. MATERIAL AND METHODS: We identified all patients who were under the age of 18 years at the time of their penetrating keratoplasty. We then assessed the electronic file on indications, graft failure, visual acuity, enucleation and further complications. RESULTS: A total of 104 eyes of 95 patients (54 % female) were identified. Median age at the time of surgery was 14 years (quartiles 8 and 16 years). Median follow-up was 2.7 years. The following indications were identified: keratoconus (39 %), penetrating injury (18 %), non-herpetic corneal scars (12 %), herpetic corneal scars (6 %), sclerocornea (3 %), chemical burn (3 %) and miscellaneous indications (19 %). Clear graft survival according to the Kaplan-Meier method ranged from 100 % (keratoconus) to 35 % (sclerocornea). Enucleation was only necessary in patients with penetrating injuries (n = 2). Kaplan-Meier analysis estimated the failure of all grafts after one year in infants. In older patients, 90 % of grafts were still clear at that time. CONCLUSION: Prognosis of penetrating keratoplasty in children is related to the indication, and therefore the underlying disease, as well as the patients' age. In particular, infants exhibited poor prognosis, with only a very short period of clear graft survival. In indications, keratoconus showed the best prognosis, whereas sclerocornea and penetrating injuries had the worst prognosis.

[Peri-ocular Necrotising Fasciitis - Case Report and Overview]. / Periokuläre nekrotisierende Fasziitis ­ Fallbericht und Überblick.

Peri-ocular necrotising fasciitis is a very rare ophthalmological clinical picture and is potentially fatal. This disease is caused by bacterial infection of the fasciae, which rapidly spreads. The present article reports a typical case of the disease and gives an overview of the typical clinical signs and symptoms of peri-ocular necrotising fasciitis.

[Diagnosis and treatment of the watering eye]. / Diagnose und Behandlung des tränenden Auges.

The wet eye is a common symptom that ophthalmologists as well as otorhinolaryngolists are confronted with. The causes can be diverse, affecting all parts from the lacrimal gland to the lacrimal drainage system. Frequently tear film changes are the reason for the symptoms, which may vary from classic epiphora and impaired vision to tear film instability with damage of the corneal epithelium. The knowledge and understanding of the underlying pathologies and differential diagnosis is crucial in order to initiate adequate therapy and to avoid overtreating with invasive surgical means.

[Seasonal and Perennial Allergic Rhinoconjunctivitis]. / Die saisonale und perenniale allergische Rhinokonjunktivitis.

Seasonsal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) as well as intermittent and persistent allergic rhinitis are widespread diseases. Because a combined occurrence of ocular and nasal symptoms is very common the summarising term allergic rhinoconjunctivitis is frequently used. SAC and PAC representing the two acute forms of allergic conjunctivitis account for more than 90% of all cases of allergic conjunctivitis. Compared to the chronic forms of allergic conjunctivitis their course of disease is milder. Nevertheless because of their high prevalence and the proven influence on patients' quality of life they possess clinical and socioeconomic relevance. Allergic rhinoconjunctivitis is caused by a type 1 IgE-mediated hypersensitivitity reaction that is provoked by aeroallergens in the majority of cases. The pathognomonic sign is itching. Besides, typical ocular findings are chemosis, conjunctival injection,watery secretion and lid swelling. Otorhinolaryngologists' findings include rhinorrhea, postnasal drip and sneezing. Problems in breathing through the nose resulting from nasal obstruction can cause impaired nighttime sleep and daytime somnolence. In addition to a reduction of allergen exposure by modification of environment and life style factors, in mild forms of SAC and PAC artificial tears are recommended. Topical antihistamines can generate rapid relief from acute symptoms and itching. Topical mast cell stabilisers however provide long-term effects. Dual action drugs that combine antihistamines and mast cell stabilisers show increased patient compliance due to reduced application frequency. Use of topical steroids should be cautious and only temporary. For prolonged treatment periods unpreserved anti-allergic eye-drops should be preferred. Combined topical antihistamines and new-generation topical nasal steroids often used by otorhinolaryngologists demonstrate a good safety profile without systemic side effects. In summary, allergic rhinoconjunctivitis represents a common disease pattern that can be treated effectively. Once it is diagnosed correctly targeted treatment results in improved patients' quality of life quickly.

Analyzing Collaborative Governance Through Social Network Analysis: A Case Study of River Management Along the Waal River in The Netherlands.

Until recently, governmental organizations played a dominant and decisive role in natural resource management. However, an increasing number of studies indicate that this dominant role is developing towards a more facilitating role as equal partner to improve efficiency and create a leaner state. This approach is characterized by complex collaborative relationships between various actors and sectors on multiple levels. To understand this complexity in the field of environmental management, we conducted a social network analysis of floodplain management in the Dutch Rhine delta. We charted the current interorganizational relationships between 43 organizations involved in flood protection (blue network) and nature management (green network) and explored the consequences of abolishing the central actor in these networks. The discontinuation of this actor will decrease the connectedness of actors within the blue and green network and may therefore have a large impact on the exchange of ideas and decision-making processes. Furthermore, our research shows the dependence of non-governmental actors on the main governmental organizations. It seems that the Dutch governmental organizations still have a dominant and controlling role in floodplain management. This challenges the alleged shift from a dominant government towards collaborative governance and calls for detailed analysis of actual governance.

[Keratomycosis - Therapy Standards and New Developments]. / Keratomykose - Therapiestandards und aktuelle Entwicklungen.

Mycotic keratitis is a comparatively rare but serious ophthalmological disease, that can possibly lead to a severe loss of vision up to blindness. Over the last two decades an increase of cases with mycotic keratitis has been noticed, which is possibly caused by an increased use of soft contact lenses. This article gives an overview of the typical clinical signs and symptoms of keratomycosis, tried and tested diagnostics and therapy as well as new diagnostic and therapeutic developments and findings.

Clinical study of therapeutic ocular surface medium for persistent epithelial defect.

PURPOSE: To investigate therapeutic ocular surface medium (TOSM), a potential physiological tear replacement therapy, for persistent epithelial defect (PED). METHODS: 11 eyes of 10 patients with PED for ≥ 2 weeks without improvement despite conventional treatment were enrolled in a prospective pilot study of TOSM over 1 month. RESULTS: Healing of the PED occurred in 3 out of the 11 eyes at 1, 2 and 4 weeks, respectively. At week 4, 2 eyes were almost healed (PED area ≤ 0.5 mm(2)). In 4 of the remaining 6 eyes, the PED area was reduced. Failure occurred in 1 case with end-stage ocular cicatricial pemphigoid and severe dry eye, and 1 patient withdrew due to a mild allergic reaction. There were no serious or irreversible side effects with TOSM. CONCLUSIONS: TOSM is a potential novel physiological therapy for PED that, unlike autologous serum, has the potential to be easily manufactured and widely available.

[Factors influencing the measurement of tear film lipid layer thickness with interferometry]. / Einflussfaktoren auf die Messung der Lipidschichtdicke des Tränenfilms mittels Interferometrie.

INTRODUCTION: The quantitative measurement of the tear film lipid layer thickness is a relatively new and promising method. However, so far it has not been investigated whether there is a diurnal or a day to day variability and whether certain factors are confounding the measurement of the lipid layer thickness. MATERIALS AND METHODS: In three different experimental settings, 10 subjects without known sicca syndrome were examined at three different time points on one day, on three different days and before and after therapeutic expression of the Meibomian glands. As a comparison, the parameters tear film break-up time, tear meniscus height, diagnostic expression of the Meibomian glands and subjective symptoms, determined using the OSDI (ocular surface disease index) questionnaire, were measured. RESULTS: The results of the study showed a smaller variation of the lipid layer thickness measurements during the day and from day to day compared to the tear film break-up time. The expression of the Meibomian glands significantly increased the lipid layer thickness. There was a correlation between the baseline values of tear film break-up time and the lipid layer thickness. DISCUSSION: Our data showed that the lipid layer thickness as measured with the Lipiview® interferometer appears to be a relatively constant parameter over time. In addition, the expression of the Meibomian glands could be identified as a potential confounding factor. In this study we included only healthy subjects without known sicca syndrome. For the future our findings need to be validated in dry eye patients.

[Seasonal and perennial allergic rhinoconjunctivitis]. / Die saisonale und perenniale allergische Rhinokonjunktivitis.

Seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) as well as intermittent and persistent allergic rhinitis are widespread diseases. Because a combined occurrence of ocular and nasal symptoms is very common the summarising term allergic rhinoconjunctivitis is frequently used. SAC and PAC representing the two acute forms of allergic conjunctivitis account for more than 90 % of all cases of allergic conjunctivitis. Compared to the chronic forms of allergic conjunctivitis their course of disease is milder. Nevertheless because of their high prevalence and the proven influence on patients' quality of life they possess clinical and socioeconomic relevance. Allergic rhinoconjunctivitis is caused by a type 1 IgE-mediated hypersensitivity reaction that is provoked by aeroallergens in the majority of cases. The pathognomonic sign is itching. Besides, typical ocular findings are chemosis, conjunctival injection, watery secretion and lid swelling. Otorhinolaryngologists' findings include rhinorrhea, postnasal drip and sneezing. Problems in breathing through the nose resulting from nasal obstruction can cause impaired nighttime sleep and daytime somnolence. In addition to a reduction of allergen exposure by modification of environment and life style factors, in mild forms of SAC and PAC artificial tears are recommended. Topical antihistamines can generate rapid relief from acute symptoms and itching. Topical mast cell stabilisers however provide long-term effects. Dual action drugs that combine antihistamines and mast cell stabilisers show increased patient compliance due to reduced application frequency. Use of topical steroids should be cautious and only temporary. For prolonged treatment periods unpreserved anti-allergic eye-drops should be preferred. Combined topical antihistamines and new-generation topical nasal steroids often used by otorhinolaryngologists demonstrate a good safety profile without systemic side effects. In summary, allergic rhinoconjunctivitis represents a common disease pattern that can be treated effectively. Once it is diagnosed correctly targeted treatment results in improved patients' quality of life quickly.

[ChatGPT and the German board examination for ophthalmology: an evaluation]. / ChatGPT und die deutsche Facharztprüfung für Augenheilkunde: eine Evaluierung.

PURPOSE: In recent years artificial intelligence (AI), as a new segment of computer science, has also become increasingly more important in medicine. The aim of this project was to investigate whether the current version of ChatGPT (ChatGPT 4.0) is able to answer open questions that could be asked in the context of a German board examination in ophthalmology. METHODS: After excluding image-based questions, 10 questions from 15 different chapters/topics were selected from the textbook 1000 questions in ophthalmology (1000 Fragen Augenheilkunde 2nd edition, 2014). ChatGPT was instructed by means of a so-called prompt to assume the role of a board certified ophthalmologist and to concentrate on the essentials when answering. A human expert with considerable expertise in the respective topic, evaluated the answers regarding their correctness, relevance and internal coherence. Additionally, the overall performance was rated by school grades and assessed whether the answers would have been sufficient to pass the ophthalmology board examination. RESULTS: The ChatGPT would have passed the board examination in 12 out of 15 topics. The overall performance, however, was limited with only 53.3% completely correct answers. While the correctness of the results in the different topics was highly variable (uveitis and lens/cataract 100%; optics and refraction 20%), the answers always had a high thematic fit (70%) and internal coherence (71%). CONCLUSION: The fact that ChatGPT 4.0 would have passed the specialist examination in 12 out of 15 topics is remarkable considering the fact that this AI was not specifically trained for medical questions; however, there is a considerable performance variability between the topics, with some serious shortcomings that currently rule out its safe use in clinical practice.

[Therapy for systemic metabolic disorders based on the detection of basic corneal landmarks in childhood]. / Hornhaut-Schlüsselbefunde im Kindesalter als Hinweis für therapierbare systemische Stoffwechselerkrankungen.

Many systemic lysosomal storage disorders show basic corneal opacities already in childhood. The lysosome is a cell organelle, produced by Golgi's apparatus, that is surrounded by a membrane and contains hydrolytic enzymes that break down food molecules, especially proteins and other complex molecules. The ophthalmologist's precise diagnosis of corneal clouding at the slit-lamp may reveal the correct interpretation of the specific lysosomal storage disorder. It is very important to diagnose such diseases as soon as possible because today the development of systemic enzymatic therapies has broadened the therapeutic armamentarium for the current standard of care. The following corneal landmarks of systemic storage diseases and of the modern systemic therapy are presented: cornea verticillata in Fabry's disease, periodic infusion of alpha-galactosidase a; Kayser-Fleischer's ring in Wilson's disease, zinc, trienetin, low copper diet; multiple, punctiform crystals in cystinosis, cysteamine, Raptor RP 103(DR cysteamine) that reduces the cytotoxity in form of continous dissolving of cystine from lysosome, renal transplantation, haematopoietic stem cell transplantation; peripheral ring, but not true lipid arc, and moderate stromal haze in LCAT-deficiency, injection of recombinant enzyme or of encapsulated LCAT-secreting cells; diffuse stromal haze in mucopolysaccharidoses (MPS). Enzyme replacement therapy is currently indicated for MPS I, MPS II, and MPS VI, haematopoietic stem cell transplantation; painful, bilateral pseudo-dendritic opacities in tyrosinemia type II (eponym: Richner-Hanhart syndrome), low phenylalanine and tyrosine diet result in complete disappearance of corneal alterations with a consecutive painfree period. Strict diet during the whole life is necessary to prevent corneal recurrences and the occurrence of palmo-plantar keratoses. Such therapies can enable the patient to lead an otherwise normal life for decades.