Changing paradigm of sacral neuromodulation and external anal sphincter repair for faecal incontinence in specialist centres.

AIM: The aim of this study was to determine whether the paradigm of surgical intervention for faecal incontinence (FI) has changed between 2000 and 2013. METHOD: This was a multi-centre retrospective study of patients who had undergone either sacral neuromodulation (SNM) or delayed sphincter repair or sphincteroplasty (SR) as a primary surgical intervention for FI in five centres in Europe and one in the United States. The flow of patients according to the intervention, sustainability of the treatment at a minimum follow-up of 5 years, complications and requirement for further interventions were recorded. RESULTS: A total of 461 patients (median age 56 years, range 24-90 years, 41 men) had either SNM or SR as an index operation during the study period [SNM 284 (61.6%), SR 177 (38.4%)]. Among SNM patients, there were 169 revisional operations (change of battery and/or lead, re-siting or removal). At the time of last follow-up 203 patients (71.4%) continued to use SNM. Among SR patients, 30 (16.9%) had complications, most notably wound infection (22, 12.4%). During follow-up 32 patients (18.1%) crossed over to SNM. Comparing two 4-year periods (2000-2003 and 2007-2010), the proportion of patients operated on who had a circumferential sphincter defect of less than 90° was 48 (68%) and 45 (46%), respectively (P = 0.03), while those who had SNM as the primary intervention increased from 29% to 89% (P < 0.05). CONCLUSION: The paradigm of surgical intervention for FI has changed with increasing use of SNM.

Ventral rectopexy with biological mesh for recurrent disorders of the posterior pelvic organ compartment.

PURPOSE: Recurrent prolapse of the posterior pelvic organ compartment presents a management challenge, with the best surgical procedure remaining unclear. We present functional outcome and patient satisfaction after laparoscopic and robotic ventral mesh rectopexy (VMR) with biological mesh in patients with recurrence. METHODS: We analyzed data from 30 patients with recurrent posterior pelvic organ prolapse who underwent VMR with biological mesh from August 2012 to January 2018. Data included patient demographics and intra- and postoperative findings; functional outcome as assessed by Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), and Cleveland Clinic Incontinence Score (CCIS); and patient satisfaction. RESULTS: CCCS, CCIS, and ODS were significantly improved at 6-12 months postoperatively and at last follow-up. Patient satisfaction (visual analog scale [VAS] 6.7 [0 to 10]), subjective symptoms (+ 3.4 [scale - 5 to + 5]), and quality of life improvement (+ 3.0 [scale from - 5 to + 5]) were high at last follow-up. The rates of morbidity and major complications were 13% and 3%, respectively. There were no mesh-related complications or deaths. Difference in type of previous surgery (abdominal or transanal/perineal) had no significant effect on results. CONCLUSIONS: VMR with biological mesh is a safe and effective option for patients with recurrent posterior pelvic organ prolapse. It reduces functional symptoms, has a low complication rate, and promotes patient satisfaction.

A second KRT71 allele in curly coated dogs.

Major characteristics of coat variation in dogs can be explained by variants in only a few genes. Until now, only one missense variant in the KRT71 gene, p.Arg151Trp, has been reported to cause curly hair in dogs. However, this variant does not explain the curly coat in all breeds as the mutant 151 Trp allele, for example, is absent in Curly Coated Retrievers. We sequenced the genome of a Curly Coated Retriever at 22× coverage and searched for variants in the KRT71 gene. Only one protein-changing variant was present in a homozygous state in the Curly Coated Retriever and absent or present in a heterozygous state in 221 control dogs from different dog breeds. This variant, NM_001197029.1:c.1266_1273delinsACA, was an indel variant in exon 7 that caused a frameshift and an altered and probably extended C-terminus of the KRT71 protein NP_001183958.1:p.(Ser422ArgfsTer?). Using Sanger sequencing, we found that the variant was fixed in a cohort of 125 Curly Coated Retrievers and segregating in five of 14 additionally tested breeds with a curly or wavy coat. KRT71 variants cause curly hair in humans, mice, rats, cats and dogs. Specific KRT71 variants were further shown to cause alopecia. Based on this knowledge from other species and the predicted molecular consequence of the newly identified canine KRT71 variant, it is a compelling candidate causing a second curly hair allele in dogs. It might cause a slightly different coat phenotype than the previously published p.Arg151Trp variant and could potentially be associated with follicular dysplasia in dogs.

Permacol™ collagen paste for cryptoglandular and Crohn's anal fistula.

BACKGROUND: Permacol™ collagen paste, an acellular crosslinked porcine dermal collagen matrix suspension, is a new treatment option for anal fistula. Data remain limited, however, and as yet only the results of one case of Crohn's fistula treated with Permacol™ paste has been reported. The aim of this study was to assess the use of Permacol™ collagen paste in patients with cryptoglandular and Crohn's perianal fistulae. METHODS: A prospective study was conducted on patients with anal fistula, treated with Permacol™ paste. Patients were followed at 1 week, 6 and 12 months, and on demand thereafter. The main focus was on fistula healing and postoperative continence. The former was defined as the absence of signs of recurrence on clinical examination, proctoscopy and rigid rectoscopy. Fecal incontinence was assessed before surgery and at each follow-up. RESULTS: Thirty patients (19 women, 11 men; mean age 46 years), 12 (40%) of whom had Crohn's disease were included. The average number of previous fistula operations was 6. All patients had ≥ 6 months of follow-up, and 24 patients (80%) had ≥ 12 months of follow-up. The healing rate in all patients was 57% (17 of 30 patients) at 6 months and 63% (15 of 24 patients) at 12 months. One patient reported a worsening of fecal incontinence at 12 months; 2 patients had adverse events (perianal pain: n = 1, fluid accumulation n = 1) requiring fistula drainage. Patient characteristics, healing, incontinence, and adverse events did not differ significantly between patients with and without Crohn's disease. CONCLUSIONS: Our data indicate that Permacol™ paste is a safe and moderately effective treatment for cryptoglandular and Crohn's fistulae.

Ventral rectopexy with biological mesh: short-term functional results.

PURPOSE: Ventral mesh rectopexy (VMR) is an established, minimally invasive, nerve-sparing procedure for the treatment of various symptomatic morphological changes in the posterior pelvic compartment. We present the short-term functional outcome and patient satisfaction after laparoscopic and robotic VMR with biological mesh. METHODS: We analyzed data from 123 patients who underwent laparoscopic ventral mesh rectopexy (LVMR) or robotic ventral mesh rectopexy (RVMR) from August 2012 to January 2017. Included in these data were patient demographics, intra- and postoperative findings, Cleveland Clinic Constipation Score (CCCS), Obstructed Defecation Score Longo (ODS), Cleveland Clinic Incontinence Score (CCIS), and patient satisfaction as measured by visual analog scale (0-10). RESULTS: Improvements in CCCS, CCIS, and ODS were statistically significant at 6 and 12 months (p < 0.001). Patient satisfaction was excellent at 6 and 12 months (8.2/10 and 8.3/10, respectively). The overall complication rate was 14%, with a major complication rate of 2%. No mesh-related complications were observed. The need for surgical re-intervention because of relapse, symptom persistence or recurrence, or new symptoms was 3%. Outcome appears to be similar between LVMR and RVMR. CONCLUSIONS: Both LVMR and RVMR with biological mesh are safe and effective in reducing symptoms, as measured by CCCS, CCIS, and ODS, and patient satisfaction is high.

A splice site variant in the SUV39H2 gene in Greyhounds with nasal parakeratosis.

Hereditary nasal parakeratosis (HNPK), described in the Labrador Retriever breed, is a monogenic autosomal recessive disorder that causes crusts and fissures on the nasal planum of otherwise healthy dogs. Our group previously showed that this genodermatosis may be caused by a missense variant located in the SUV39H2 gene encoding a histone 3 lysine 9 methyltransferase, a chromatin modifying enzyme with a potential role in keratinocyte differentiation. In the present study, we investigated a litter of Greyhounds in which six out of eight puppies were affected with parakeratotic lesions restricted to the nasal planum. Clinically and histologically, the lesions were comparable to HNPK in Labrador Retrievers. Whole genome sequencing of one affected Greyhound revealed a 4-bp deletion at the 5'-end of intron 4 of the SUV39H2 gene that was absent in 188 control dog and three wolf genomes. The variant was predicted to disrupt the 5'-splice site with subsequent loss of SUV39H2 function. The six affected puppies were homozygous for the variant, whereas the two non-affected littermates were heterozygous. Genotyping of a larger cohort of Greyhounds revealed that the variant is segregating in the breed and that this breed might benefit from genetic testing to avoid carrier × carrier matings.

Prevalence of upper extremity pain in a population of people with paraplegia.

STUDY DESIGN: Cross-sectional study. OBJECTIVES: To determine the prevalence, patterns, and predictors of musculoskeletal pain in the upper extremity joints among wheelchair-dependent individuals with post-traumatic paraplegia. Secondarily, to document most common reported causes of upper extremity pain. SETTING: Centre for Orthopaedics, Trauma Surgery and Spinal Cord Injury, Germany. METHODS: The study was done by means of a structured questionnaire, which was mailed to the individuals who had been treated between 1990 and 2007 for newly sustained or pre-existing, accident-related paraplegia (n = 670). The questionnaire was designed mainly to obtain the information regarding shoulder, elbow, and wrist pain. Additional data included participant demographics, mechanism, level and completeness of injury as well as wheelchair dependence and time since injury. The Frankel classification system was used to define the completeness of injury. RESULTS: Four hundred and fifty-one (67%) questionnaires were included. Pain was reported by approximately 81% of the participants. Of this sample, 61% had shoulder pain, 33% had elbow pain, and 43% had wrist pain, 19% had shoulder, elbow, and wrist pain, 27% had shoulder and elbow pain, 34% had shoulder and wrist pain, 21% had elbow and wrist pain. The main diagnoses were rotator cuff tears for individuals with shoulder pain, epicondylitis for those with elbow pain, and carpal tunnel syndrome for those with wrist pain. The development of shoulder/elbow and wrist pain correlated with age and time since injury. CONCLUSIONS: Age and the length of time since injury correlated with a higher rate of shoulder, elbow, and wrist pain. The completeness of injury, neurological level, and gender were correlated with shoulder, elbow, and wrist pain, respectively.

Effectiveness of sacral nerve stimulation in fecal incontinence after multimodal oncologic treatment for pelvic malignancies: a multicenter study with 2-year follow-up.

BACKGROUND: To assess whether sacral nerve stimulation (SNS) is an effective treatment for severe fecal incontinence (FI) after radiotherapy (RT)/chemoRT (CRT) in combination with pelvic surgery. METHODS: A multicenter study was conducted on patients with FI that developed after multimodal therapy for pelvic tumors and was refractory to non-operative management, who were treated with SNS between November 2009 and November 2012. Data were prospectively collected and retrospectively analyzed. Cleveland Clinic FI score (CCFIS), FI episodes per week, FI Quality of Life (FIQoL), anorectal manometry and pudendal nerve terminal motor latency were evaluated before and after SNS. RESULTS: Eleven patients (seven females, mean age 67.3 ± 4.8 years) were evaluated in the study period. Multimodal treatments included surgery and CRT (four rectal, two cervical and one prostate cancers), surgery and RT (one cervical and two endometrial cancers) and CRT (one anal cancer). The mean radiation dose was 5.3 Gy, and mean interval between the end of RT and onset of FI was 43.7 ± 23 months. Before SNS, the mean CCFIS and the mean number of FI episodes per week were 15.7 ± 2.8 and 12.3 ± 4.2, respectively. At 12-month follow-up, mean CCFIS improved to 3.6 ± 1.8 (p = 0.003) and the mean number of FI episodes decreased to 2.0 ± 1.9 per week (p = 0.003). These results persisted at 24-month follow-up. Significant improvement was also observed for each of the four domains of FIQoL at 12- and 24-month follow-up. Anorectal manometry values did not change significantly at follow-up. CONCLUSIONS: SNS is feasible and may be an effective therapeutic option for FI after multimodal treatment of pelvic malignancies.

[Risk factors for the development of rotator cuff tears in individuals with paraplegia : A cross-sectional study]. / Risikofaktoren für Rotatorenmanschettenrupturen bei Paraplegikern : Eine Querschnittstudie.

QUESTION: Shoulder pain and rotator cuff tears are highly prevalent among wheelchair dependent individuals with paraplegia. The purpose of this study was to identify potential risk factors associated with the development of rotator cuff tears in this population. METHODS: A total of 217 wheelchair dependent individuals with paraplegia were included in this cross-sectional study (level of evidence III). The mean age of this population was 47.9 years and the mean duration of wheelchair dependence was 24.1 years. Each individual was asked to complete a questionnaire designed to identify risk factors for rotator cuff tears and underwent a standardized clinical examination with the documentation of the Constant-Murley shoulder outcome score and magnetic resonance imaging (MRI) of both shoulder joints. RESULTS: MRI analysis revealed at least one rotator cuff tear in 93 patients (43%). Multiple logistic regression analysis identified the following factors to be associated with the presence of rotator cuff tear: patient age, duration of spinal cord injury/wheelchair dependence, gender, and wheelchair athletic activity. Neither BMI nor the level of spinal cord injury was found to pose a risk factor in the population studied. With respect to patient age, the risk of developing a rotator cuff tear increased by 11% per annum. In terms of duration of spinal cord injury, the analysis revealed a 6% increased risk per year of wheelchair dependence (OR = 1.06). Females had a 2.6-fold higher risk of developing rotator cuff tears than males and wheelchair sport activity increased the risk 2.3-fold. DISCUSSION: There is a high prevalence of rotator cuff tears in wheel-chair dependent persons with paraplegia. Risk factors such as age, gender, duration of paraplegia, and wheel chair sport activity seem to play an important role in the development of rotator cuff tears.

Sacral nerve stimulation for faecal incontinence in patients with sacral malformation.

INTRODUCTION: Sacral nerve stimulation (SNS) is a common and effective treatment for faecal incontinence (FI), but accessibility of the sacral nerves is mandatory. In some cases, electrode placement fails for unknown reasons. A frequent cause could be sacral malformations, which have a high incidence (up to 24.1%) and can be unsuspected. METHODS AND RESULTS: We report two patients with FI consequent to congenital anorectal malformation and associated sacral malformation. Despite partial sacral agenesis, SNS was feasible in both. They benefitted greatly from SNS, with an improved ability to postpone the urge up to at least 15 min, reduced incontinence episodes (at least 50%), and significantly better quality of life. CONCLUSION: SNS may be feasible in patients with FI, even in the presence of sacral malformation. However, clinicians should be aware of the attendant technical difficulties. Preoperative imaging, preferably with MRI of the sacrum, is advisable. If the sacral spinal nerves are inaccessible technically, pudendal nerve stimulation could be considered, if anatomy permits.

Benign atrophic papulosis (Köhlmeier-Degos disease): the wedge-shaped dermal necrosis can resolve with time.

BACKGROUND: Atrophic papulosis is a rare thrombo-occlusive disease, characterized by the appearance of multiple atrophic porcelain-white skin papules, with a surrounding erythematous rim, which are histologically consisting of wedge-shaped necrosis of the dermis. OBJECTIVE: It consists of two variants: (i) the benign atrophic papulosis (BAP) only involving the skin and (ii) the malignant atrophic papulosis (MAP) also involving several internal organs with a cumulative five-year survival rate of approx. 55%. While the probability of only having a BAP at onset is approximately 70%, increasing to 97% after 7 years of monosymptomatic cutaneous course, no close long-term follow-up of the development of the skin lesions has been reported. METHODS: We present a precise visual documentation of the evolution of the disseminated skin lesions in a female patient with BAP spanning over two decades. RESULTS: A considerable improvement and/or clinical resolution of the majority of the lesions disputing the scarring character of the atrophic porcelain-white skin papules has been detected. CONCLUSION: BAP not only exhibits an excellent prognosis, but resolution of lesions can also occur after a considerable period of time.

Tribes and tribulations: interdisciplinary eHealth in providing services for people with a traumatic brain injury (TBI).

BACKGROUND: eHealth has potential for supporting interdisciplinary care in contemporary traumatic brain injury (TBI) rehabilitation practice, yet little is known about whether this potential is being realised, or what needs to be done to further support its implementation. The purpose of this study was to explore health professionals' experiences of, and attitudes towards eHealth technologies to support interdisciplinary practice within rehabilitation for people after TBI. METHODS: A qualitative study using narrative analysis was conducted. One individual interview and three focus groups were conducted with health professionals (n = 17) working in TBI rehabilitation in public and private healthcare settings across regional and metropolitan New South Wales, Australia. RESULTS: Narrative analysis revealed that participants held largely favourable views about eHealth and its potential to support interdisciplinary practice in TBI rehabilitation. However, participants encountered various issues related to (a) the design of, and access to electronic medical records, (b) technology, (c) eHealth implementation, and (d) information and communication technology processes that disconnected them from the work they needed to accomplish. In response, health professionals attempted to make the most of unsatisfactory eHealth systems and processes, but were still mostly unsuccessful in optimising the quality, efficiency, and client-centredness of their work. CONCLUSIONS: Attention to sources of disconnection experienced by health professionals, specifically design of, and access to electronic health records, eHealth resourcing, and policies and procedures related to eHealth and interdisciplinary practice are required if the potential of eHealth for supporting interdisciplinary practice is to be realised.

[Interdisciplinary position paper "Perioperative pain management"]. / Interdisziplinäres Positionspapier "Perioperatives Schmerzmanagement".

Despite many positive developments, postoperative pain and its treatment is still not always given the necessary attention. Severe pain after surgical procedures affects a significant proportion of patients. This very fact is not only detrimental to the immediate recovery process, but can also form the basis for the development of chronic pain conditions.An adequate and effective management of perioperative pain requires appropriate organizational structures. This multidisciplinary paper which was initiated by the Austrian Society for Anaesthesiology and Intensive Care and the Austrian Pain Society and developed together with numerous specialist and professional societies dealing with the subject aims at supporting the organization of perioperative pain management structures and to make best use of proven concepts. Additional recommendations describe specific interventions for selected types of intervention.

[Two annular, atrophic plaques on the abdomen of a 35-year-old man]. / Zwei anuläre, atrophische Plaques am Abdomen bei einem 35-jährigen Patienten.

A 35-year-old man presented with two annular, reddish-brown, atrophic skin lesions in the navel and on the right lower abdomen. The lesions had persisted for more than 4 years and had remained unchanged and asymptomatic. Histology revealed annular atrophic lichen planus with a lichenoid lymphocytic infiltration and cystoid bodies. The patient was treated with local corticosteroids without improvement.

Effects of neratinib and combination with irradiation and chemotherapy in head and neck cancer cells.

OBJECTIVE: Prognosis of patients with head and neck squamous cell carcinoma (HNSCC) is still poor. Novel therapeutic approaches are of great interest to improve the effects of radiochemotherapy. We evaluated the effects of tyrosine kinase inhibitor neratinib on HNSCC cell lines CAL27, SCC25 and FaDu as a single agent and in combination with irradiation and chemotherapy. METHODS: Effects of neratinib were evaluated in HNSCC cell lines CAL27, SCC25 and FaDu. Effect on cell viability of neratinib and combination with cisplatin and irradiation was measured using CCK-8 assays and clonogenic assays. Western blot analysis was performed to distinguish the effect on epithelial growth factor receptor and HER2 expression. Apoptosis was evaluated by flow cytometry analysis. RESULTS: Growth inhibition was achieved in all cell lines, whereas combination of cisplatin and neratinib showed greater inhibition than each agent alone. Apoptosis was induced in all cell lines. Combination of neratinib with irradiation or cisplatin showed significantly increased apoptosis. In clonogenic assays, significant growth inhibition was observed in all investigated cell lines. CONCLUSION: Neratinib, as a single agent or in combination with chemo-irradiation, may be a promising treatment option for patients with head and neck cancer.

[Robotic-Assisted Liver Surgery]. / Roboterassistierte Leberchirurgie.

BACKGROUND: The advantages of minimally invasive liver resections for selected patients are evident. Robots provide new innovations that will influence minimally invasive liver surgery in the future. This article presents our initial experience with this technology in our patient population. Material und Methods: In 14 patients with benign or malignant liver tumours, robotic-assisted liver surgery was performed. Selection criteria were compensated liver function and resection of ≤ 3 liver segments. Chronic liver disease or previous abdominal surgery were no exclusion criteria. RESULTS: Malignant liver tumours were removed in 10 patients (71%) and benign symptomatic liver tumors in 3 patients (21%), respectively, with histopathologically negative margins (R0). One patient suffering from HCC underwent intraoperative ablation. In one case (7%) conversion was necessary. Mean operation time was 296 min (120-458 min); mean estimated blood loss was 319 ± 298 ml. The mean hospital stay of the patients was 8 days (3-17 days). Three patients (21%) suffered from postoperative complications, which were manageable by conservative treatment (Clavien-Dindo I) in 2 cases (14%). One patient (7%) needed endoscopic treatment for postoperative bile leak (Clavien-Dindo III a). No patient died intra- or perioperatively. CONCLUSION: Robotic-assisted liver surgery is a safe procedure, which provides patients with all benefits of minimally invasive surgery. This highly advanced technology requires surgeons to strive for an increasing level of specialisation, in addition to being well-trained in liver surgery. Hence, a clear definition of the procedures and standardised teaching programs are necessary.

The effect of resveratrol in combination with irradiation and chemotherapy: study using Merkel cell carcinoma cell lines.

BACKGROUND AND PURPOSE: Merkel cell carcinoma (MCC) is a rare, but highly malignant tumor of the skin. In case of systemic disease, possible therapeutic options include irradiation or chemotherapy. The aim of this study was to evaluate whether the flavonoid resveratrol enhances the effect of radiotherapy or chemotherapy in MCC cell lines. MATERIALS AND METHODS: The two MCC cell lines MCC13 and MCC26 were treated with increasing doses of resveratrol. Combination experiments were conducted with cisplatin and etoposide. Colony forming assays were performed after sequential irradiation with 1, 2, 3, 4, 6, and 8 Gy and apoptosis was assessed with flow cytometry. Expression of cancer drug targets was analyzed by real-time PCR array. RESULTS: Resveratrol is cytotoxic in MCC cell lines. Cell growth is inhibited by induction of apoptosis. The combination with cisplatin and etoposide resulted in a partially synergistic inhibition of cell proliferation. Resveratrol and irradiation led to a synergistic reduction in colony formation compared to irradiation alone. Evaluation of gene expression did not show significant difference between the cell lines. CONCLUSION: Due to its radiosensitizing effect, resveratrol seems to be a promising agent in combination with radiation therapy. The amount of chemosensitizing depends on the cell lines tested.

[Generalized inflammatory epidermolysis bullosa acquisita initially diagnosed as viral exanthem: a rare disease within the subepidermal blistering disorders]. / Generalisierte inflammatorische Epidermolysis bullosa acquisita bei initialem Virusexanthemverdacht: Eine seltene Erkrankung innerhalb der erworbenen blasenbildenden Dermatosen.

A 67-year-old man presented with a maculopapular exanthem which started over the major joints. Within a few days, it spread to the entire skin surface and was accompanied by blisters as well as changes of the oral mucosa. The histological examination revealed subepidermal blistering. Targeted laboratory examinations detected serum antibodies against the epidermal basement membrane and autoantibodies against type VII collagen. The findings supported the diagnosis of a generalized inflammatory epidermolysis bullosa acquisita with mucosal involvement.

Control of ocular disease in mucous membrane pemphigoid.

BACKGROUND: Mucous membrane pemphigoid is a rare immune-mediated disease. It is characterised by an abnormal binding of immunoglobulins to the basement membrane zone of mucous membranes and the skin. Conjunctival involvement in mucous membrane pemphigoid may lead to cicatrising conjunctivitis and eventually to corneal blindness. The factors that determine mild or progressive disease are not fully understood and need to be clarified. This study examines the features, progression and risk factors of patients with ocular involvement in mucous membrane pemphigoid. METHODS: 36 eyes of 18 patients with the diagnosis of ocular disease associated with MMP were identified. Fornix depth and keratopathy were repeatedly assessed using a standardised protocol to identify progression. MMP was diagnosed based on the characteristic clinical and laboratory features. Endpoints of the study were the incidence of progressive disease and the development of keratopathy with and without systemic immunomodulatory therapy. RESULTS: 12 eyes of 6 patients (33%) showed progressive conjunctival cicatrisation. Obvious progression was observed in 2 patients who had refused systemic treatment at an early stage. 10 eyes showed progression while on systemic treatment. In these patients, however, systemic treatment was started at an advanced stage of the ocular disease. None of the patients receiving systemic treatment developed persistent keratopathy. CONCLUSION: Systemic treatment with diaminodiphenyl sulfone and/or cyclophosphamide allows one to control the further progression of cicatrising conjunctivitis. It prevents keratopathy. To be efficient, however, treatment has to be started at an early stage of the ocular disease.