Equine recurrent uveitis

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Acute uveitis with corneal edema and completely clouded lens in an Icelandic horse

The Equine recurrent uveitis (composed of equus = lat. "Horse", recidere = lat. "Fall back" and uveitis ), abbreviated ERU , commonly known as moon blindness or periodic eye inflammation called, one is inflammatory disease of the middle eye skin ( uvea ) of the eye in horses . It can occur on one or both sides and - in contrast to a one-off uveitis - typically recurs at different intervals, i.e. recurring, or chronically insidious. The function of the eye is increasingly impaired in the course of ERU due to damage to the internal eye structures. Especially if the disease is not treated, it can lead to complete blindness within a short time . A cure of the ERU is not possible. Current therapeutic approaches therefore aim to preserve the eyesight of the affected eye as well as possible and to reduce the inflammatory processes in the eye.

Although in many cases of ERU an infection of the eye with bacteria of the genus Leptospira , i.e. leptospirosis, can be determined, it is now assumed that ERU is not directly or at least partially due to this infection. Current research results led to the now scientifically accepted hypothesis that ERU is an immune-associated disease of various causes.

The ERU is one of the most important diseases of the horse and is of great veterinary importance as the most common eye disease in horses. Around 8 to 12% of the horses in the global horse population (consisting of domestic horses , leisure horses , work horses and sport horses ) become ill. The economic and legal importance of the ERU is still very high. Under the designation "Periodic eye inflammation", the ERU belonged to the main warranty defects in horses defined in the Imperial Cattle Deficiency Ordinance of 1899 until the reform of the law of obligations of the BGB on January 1, 2002 .

Veterinary importance

Past and present veterinary research and the resulting publications on the ERU usually focus on domesticated horses. In earlier times the horse had a high socio-economic importance as a livestock and working animal, which was present in far greater numbers than it is today, which today is only found in professional sport horses. Despite the sharp decrease in the number of farm horses due to industrialization, the importance of the horse industry as an economic factor is still high and accordingly horses are the subject of intensive veterinary research.

ERU is widespread worldwide and is the predominant cause of acquired blindness in horses. Estimates of the infestation rate range from around 7.6% to 12% of the global horse population. Gilger and Michau estimate an infestation rate of 8% for the entire horse population in the United States. According to a study, around 8% of the horse population in West Germany shows symptomatic changes that can be traced back to an ERU. Other sources estimate the infestation rate at up to 12% of the horse population.

According to a study by the Department of Horses of the Vetsuisse Faculty of the University of Zurich , ERU is the most frequently diagnosed eye disease in horses at 32%. The initial uveitis that triggers ERU can occur in animals of any age. Statistical data from a study on a total of 68 animals in the United States and Canada indicated a particularly high incidence of initial disease in horses between the ages of 4 and 6 years. According to Gilger, race is an important predisposing factor . Depending on the breed, 2 to 25% of the animals are affected. Appaloosa and Appaloosa Sport Horse are particularly susceptible horse breeds .

history

Symptoms of disease typical for ERU have been described for horses since ancient times. A likely first mention of the disease is Pliny the Elder in his Naturalis Historia attributed: "quo turpior homini inscientia est fatenti praecipue iumentorum quorundam in oculis morbos cum luna increscere ac minui." In late Roman times, in the veterinary medicine factory Digesta Artis Mulomedicinae of Flavius Vegetius Renatus first coined the term oculus lunaticus for the disease. One suspected influences of the moon cycle and saw a connection between the waning moon phase and the periodically recurring inflammation, which ultimately led to "moon blindness" in most cases. Common treatment methods at that time were local bloodletting and poultices.

Even in the Middle Ages, due to a lack of better knowledge, only different forms of blood withdrawal were used, such as cutting the eye or muzzling , in which different muscle strands in the eye area were severed and blood was withdrawn. With the general technical and scientific advances in the 18th century, the established knowledge and treatment methods relating to ERU were increasingly challenged. In the first quarter of the 19th century, works on equine ophthalmology appeared for the first time, some of which questioned the previous investigation and treatment of ERU. With the discovery of the effect of extract of belladonna as a pupil enlarging drug ( mydriatic , 1800) and in 1851 by Hermann von Helmholtz invented the ophthalmoscope , the application but only decades were established later in veterinary medicine, for the first time were instruments for a more detailed examination of the ERU available.

In accordance with the importance of the horse, especially in agriculture and the military, the frequent occurrence of the disease and the considerable restriction on the use of the affected horse, equine recurrent uveitis found its way into the jurisprudence when buying horses , especially in the 18th and 19th centuries . And so, just after the general Prussian law a 28-day return policy on occurring after buying symptoms, valid from 1794 to 1900, laid down (this also affected the Remontenankauf the military). In the imperial “Ordinance on the main defects and warranty periods in the cattle trade” in the version of March 27, 1899, the periodic eye inflammation is named as the main warranty defect under Paragraph 1, I, 5 : “5. Periodic eye inflammation (internal eye inflammation, moon blindness) with a warranty period of fourteen days; Periodic eye inflammation is the inflammatory change in the internal organs of the eye based on internal influences; " In addition, the regulations on the main warranty defects were also available in paragraphs 481 to 492 of the old version of the German Civil Code (BGB), which were valid until 31 December 2001 were valid.

etiology

The ideas of the cause of the disease ( etiology ) of the ERU have changed several times until today. In addition to the influence of the moon, other negative influences from external factors such as food, water and soil conditions, worm poisons, changing teeth or unfavorable climatic conditions were suspected to be the cause. Later, circulatory disorders in the horse's head area due to harness pressure and, according to relevant scientific discoveries, also hereditary diseases, infections or parasite infestation came into question.

SEM image of the type genus of Leptospira : L. interrogans

The initial assumption in modern veterinary medicine after the mid-20th century that the ERU is caused by an autoimmune reaction in the horse has been considered obsolete since the turn of the 20th and 21st centuries. Earlier studies by Otto Gsell from the 1940s showed for the first time a connection between the symptoms of the disease and bacteria of the genus Leptospira . The bacteria from the group of spirochetes are often ingested by horses via spoiled feed, which contains the excrement (especially urine ) of small animals such as mice. The occurrence of the disease also increases in horses that are kept in swampy areas, since leptospira are more common there. A study on 501 horses in Europe in 2000 found leptospira in 32.2% of the animals examined. Of these, 78.2% could be assigned to Leptospira kirschneri serovar Grippophytosa.

In her investigations, Wollanke found intraocular leptospirosis also caused by leptospira , here exclusively in the eyes of horses with ERU. In 52.8% of the ERU cases she examined, Leptospira could be isolated directly from the eye ( vitreous humor and aqueous humor ); in 89.7% of the cases examined, antibodies against leptospira were detected. It was therefore generally assumed that the ERU is the result of this specific bacterial disease, leptospirosis, or an allergic reaction to the protein of the leptospira or to the body's own antigens . Thus, the ERU was ultimately viewed as a likely immune-induced disease as a result of an allergic reaction in persistent intraocular leptospirosis. As recently as 2006, Gerhards and Wollanke wrote that due to the connections between the detected intraocular leptospiral infection and ERU symptoms, ERU is not an autoimmune disease , but an intraocular leptospirosis.

However, the etiology and pathogenesis of ERU are still not fully understood. In the meantime, the earlier assumption that leptospirias and the leptospirosis they cause are primarily responsible for the ERU has been questioned or at least put into perspective. The currently accepted hypothesis in veterinary medicine is that ERU is the result of an immune-associated disease, based on various causes, which manifests itself in recurrent hypersensitivity reactions at variable and often decreasing intervals. In addition to the previously favored leptospira, streptococci , viral infections, allergic reactions, autointoxications , hereditary dispositions or autoimmune complex diseases are now being discussed as possible causes of inflammatory processes in the context of ERU . According to recent research, the ERU is with the MHC class 1 - gene haplotype ELA-A9 associated. Leptospira may not be the primary triggering factor in ERU, but it is responsible for the breakdown of the blood-eye barrier and the subsequent intraocular autoimmune reactions .

Classification of the equine recurrent uveitis

Structure of the vertebrate eye

As the part of the name "uveitis" already suggests, certain parts of the horse's eye system are affected by ERU. This is summarized as the uvea or "middle eye skin". The uvea is divided into three sections: the iris (Iris), the ciliary or ciliary body ( ciliary body ) and the choroid (Choriodea, choroid).

In ERU, a distinction is made between "anterior uveitis", which primarily manifests itself in inflammation of the iris (iritis), and "posterior uveitis", in which the choroid is inflamed (choroiditis), according to the affected uveal areas. There is also an "intermediate uveitis" in which the ciliary body is inflamed (cyclitis). In veterinary medicine, however, no further differentiation is made between intermediate and posterior uveitis, as there are often combined inflammatory diseases (cyclochoroiditis). In the case of inflammatory processes in the middle and posterior areas of the uvea, the term "posterior uveitis" is used in summary. However, in many horses the differently localized inflammatory processes in the entire uvea run parallel or shifted in time, so that ultimately the entire uvea can be affected. This often occurs in advanced ERU cases, which are then referred to as "panuveitis".

The American veterinarian Gilger divides the ERU according to the following criteria: The classic ERU ('classic ERU') shows the typical symptoms and the typical relapsing course. The insidious ERU ('insidious ERU'), on the other hand, is characterized by a creeping course of the disease. Externally visible pain is absent here and the inflammatory reactions are only minor. The disease therefore leads to a long-term unnoticed destruction of internal eye structures. According to Gilger, this form of ERU is widespread in the USA, especially with the Appaloosa breed and the workhorse breeds (often cold-blooded ). The third form is called the posterior ERU ('rear ERU'). The vitreous, retina, and choroid are particularly affected, although minor signs of inflammation can also occur in the anterior sections of the uvea. Opacities in the vitreous humor, retinal detachment and loss of vision dominate. According to Gilger, warm-blooded animals and horses imported from Europe to the USA are mainly affected.

Course of disease

The course of the ERU disease can be divided into three different phases, in which the recurrent character of the disease becomes apparent. First there is a primary acute flare-up of inflammation with sudden to gradual onset of clinical symptoms. With appropriate treatment, the acute inflammatory phase subsides after a few days and is overcome after 14 days at the latest. This is followed by an inflammation-free interval, in which signs of the previous inflammatory phase can still be detected, such as corneal opacity due to the deposition of inflammation products. The inflammation-free interval until the next flare-up of inflammation is still relatively long at the beginning of an ERU, but becomes smaller and smaller as the disease progresses. A non-treatment in the inflammation phase shortens the inflammation-free period significantly. As the disease progresses, the typical recurring inflammatory attacks ( relapses ) occur. The inflammation intervals can range from a week to several years. The inflammation usually recurs after several weeks or months. While usually only one eye is initially affected, in 30 to 35% of cases the disease also spreads to the other eye. The time to complete blindness varies individually between six months and about nine years, although there are also documented cases in which no discernible symptoms remained despite repeated recurrences.

Symptoms

The clinical symptoms of ERU can be very variable depending on the affected part of the uvea. Regardless of the localization of the ERU, there are general acute symptoms of the disease that are common to both localizable forms of uveitis and, depending on the severity, can also be differently pronounced:

Sick horses are typically light-shy (photophobia) and show increased tear flow ( Epiphora ). The conjunctiva (conjunctiva) is reddened. The eyelids are often swollen and warm; the horses can suffer from severe eyelid cramps ( blepharospasm ). In the anterior chamber of the eye and on the cornea , smoky, flaky opacities (corneal edema) and - in 20 to 25% of cases - corneal abrasions can also occur. The pupils are often narrowed ( miosis ).

Because of the inflammatory processes, pain can occur, especially if there is a painful inflammation of the iris ( iritis ) as part of anterior uveitis . Pain or other conspicuous symptoms may, however, be absent or be so slight that the ERU is only noticed when severe visual disturbances are already present. This is especially the case with posterior uveitis, which is less painful to painless. The horse can suffer from a fever and can often appear listless.

Diagnosis and differential diagnosis

The diagnosis is made on the basis of the clinical picture and a documented previous episode of the disease. The latter is important for differentiating from primary (non-ERU) uveitis. In addition, other diseases associated with clouding of the eyes and eye pain such as corneal inflammation (viral or immune-related), glaucoma or stromal abscesses must be excluded. Detection of antibodies to leptospira can be helpful. If the antibody titer in the aqueous humor is higher than that in the blood serum , this indicates that antibodies are being formed in the eye.

treatment

The disease of a horse with leptospiral ERU (lERU) is curable as long as there is no severe damage to the affected eye. The causative bacteria (leptospira) are removed by means of a vitrectomy and there is a very high probability that painful and eye-damaging inflammatory attacks will no longer occur. In the case of non-leptospiral ERU (nlERU), which often occurs in tiger piebalds (Appaloosa, Knabstrupper, Criollo), an autoimmune reaction against retinal (affecting the retina) antigens is assumed. Here, further attacks of inflammation cannot be prevented, but can only be weakened with medication or depot preparations (cyclosporine implants). With nlERU, a vitrectomy is only used to remove deposits in the vitreous body and cannot prevent further flare-ups.

The acute inflammatory flare-up is treated with anti-inflammatory drugs that dilate the pupil.

General measures

A variety of factors in horse keeping can help to positively influence the course of the disease. These include, for example, a change in feed, optimization of housing conditions, consistent insect and rodent control, a reduction in solar radiation, eye protection using a UV-resistant fly mask , but also precise vaccination and deworming plans. Documented cases in horses indicate a connection between inflammatory processes in the eye and vaccination or deworming. In these cases, pre- and post-treatment of these animals with a flunixin - meglumine combination has proven to be effective, which prevents a corresponding inflammatory process in the eye relatively reliably.

Possibilities of internal and external drug treatment in ERU
drug Active ingredient group effect
Prednisolone Glucocorticoids Highly effective, anti-inflammatory,

very good eye penetration

Dexamethasone Glucocorticoids Highly effective, anti-inflammatory,

very good eye penetration

Triamcinolone Glucocorticoids anti-inflammatory, immunosuppressive,

long lasting effect

Flurbiprofen NSAID anti-inflammatory,

very good eye penetration

Flunixin - meglumine NSAID Highly effective, anti-inflammatory
Phenylbutazone NSAID anti-inflammatory
Cyclosporin A , tacrolimus Immunosuppressants strong immunosuppressive drugs, acts on

immune-mediated effects of ERU

Atropine Anticholinergic Pain relief, prevention of

Synechiae

Doxycycline Tetracyclines Antibiotic , bacteriostatic effectiveness

with leptospira

Gentamicin Aminoglycosides Antibiotic, bacteriostatic effectiveness

with leptospira

Drug therapy for equine recurrent uveitis

In the early stages of the disease, conservative treatment with an anti - inflammatory eye ointment containing cortisone or with appropriate eye drops for the affected eye is recommended. This measure is supported by the administration of systemic administration of painkillers .

In the drug treatment of an active ERU, pupil-expanding cycloplegics are administered. These paralyze the inner eye muscle, ciliary muscle , reduce inflammation-related pain and reduce the risk of adhesion ( synechia ) between the posterior surface of the cornea and the iris or anterior lens surface . In particular, corticosteroids or so-called “nonsteroidal anti-inflammatory drugs” (NSAID) are given to combat inflammation . The use of orally administered or intravenously injected flunixin meglumine as part of a systemic treatment is currently considered to be the most efficient inflammation treatment for the horse's eye. Other drugs such as phenylbutazone are either significantly less effective or, like dexamethasone or prednisolone , are only given when other anti-inflammatory drugs cannot be used or do not work.

In the case of very strong ERU attacks, the injection of corticosteroids into the conjunctiva can support the therapy, as can the application of a subpalpebral catheter for irrigation and for the permanent administration of externally applied drugs. A ciclosporin A implant has also been used for a short time . Ciclosporin A suppresses the immune reactions that occur during an ERU. The implant is placed in the diseased eye between the dermis ( sclera ) and the choroid (choroid) and continuously releases the active ingredient for up to twelve months. Although the implantation itself can be carried out with little technical effort, a vitrectomy and opening of the globe under general anesthesia are still necessary.

As a rule, a drug therapy duration of at least two weeks must be expected. After the symptoms have completely subsided, the treatment is allowed to taper off for a further period of two weeks.

Depending on the choice of medication available, there may be other and undesirable health side effects. The use of externally applied eye ointments containing cortisone can damage the cornea due to the strengthening effect of the drug on collagenases , which then attack the epithelial cells . The susceptibility of the cornea to fungal infections also increases when they are used. The administration of Cycloplegica, in particular atropine, can be responsible for colic attacks accompanying the disease . Likewise, long-term administration of drugs from the NSAID group can cause damage to the stomach and kidneys.

Many horses respond well to drug treatment with corticosteroids or NSAIDs. However, it will only have an effect on the symptoms of the current ERU attack, but not on subsequent attacks. This is where new therapeutic approaches come into play, which should generally avoid the relapsing flare-up or at least significantly reduce the intensity of a new flare-up. For example, ASA , the aforementioned phenylbutazone or herbal ingredients, especially dimethyl sulfone , are used with varying degrees of success and sometimes with negative side effects.

Combating existing leptospira in the eye with antibiotics as a way of preventing or minimizing an ERU flare comes into consideration. For this purpose, doxycycline or tetracycline is administered orally in a four-week treatment . The injection of gentamicin directly into the vitreous humor is also an efficient, but also not harmless, method for the direct control of a leptospira-induced ERU. In cases where the ERU attacks are promoted or even triggered by the presence of leptospira, the administration of antibiotics has proven to be an effective method. However, there is no long-term experience with this in research and it is also still unclear whether the proven positive effects are based directly on combating the leptospira present in the vitreous humor or on other effects.

Vitrectomy

A very efficient method of preventing further attacks of inflammation and thus further damage to the eye from the ERU is an operative vitreous exchange, the so-called vitrectomy . This is mainly carried out in Europe and less often in the USA, since the proportion of posterior and leptospira-associated ERUs is lower here. If the surgeon has the appropriate experience, vitrectomy in horses is now considered a routine procedure. In 2012 the Equine Clinic at the Ludwig Maximilians University in Munich performed 150 vitrectomies.

The vitreous humor of the affected eye is crushed and then suctioned off. At the same time, the vitreous space is filled with a special liquid to maintain intraocular pressure. After a short time, the eye itself replaces this fluid with aqueous humor. This removes inflammation products in the vitreous humor, vitreous opacities and the often causal or at least ERU-associated leptospira. As an additional effect, after the viscous vitreous material has been removed, the fluid circulation in the vitreous is improved and a new leptospiral infection is thus prevented.

The recurrence of inflammatory flare-ups during an ERU can be prevented with a probability of up to 98%. Another positive aspect is that the eyesight of the treated eye is usually better after a vitrectomy than before. However, this depends heavily on the degree of previous damage. In the case of less previously damaged eyes, vision can be improved or retained through a vitrectomy with a good prognosis. The risk of consequential damage such as the formation of a cataract is then less than 3%, the risk of retinal detachment even less than 1%. In general, in addition to cataract and retinal detachment, a vitrectomy also carries the risk of bacterial septic endophthalmitis , which always leads to blindness. However, this complication only occurs in less than 0.5% of all operations performed.

The more previous damage the eye already has from the ERU, the lower the chance of an improvement or even preservation of vision through this measure. Symptoms that severely impair the efficiency of a vitrectomy are, for example, flat posterior synechiae, incipient cataract or retinal detachment, or even atrophy of the eyeball ( phthisis bulbi ). However, here too - in individual cases even in horses that are already blind - a vitrectomy is nevertheless medically advisable in order to avoid further flare-ups and the corresponding costly veterinary treatment measures.

Equine recurrent uveitis in other members of the genus Equus

Even if the literature is limited to horses kept in human care, it can be assumed that the stocks of wild horses worldwide also suffer from the ERU.

In addition to the horses, donkeys are also affected, such as the description of the breeding goal for the European donkey breed shows: Here, an illness with periodic eye inflammation leads to an inability to breed and excludes an entry in the stallion book I for stallions and the stud book I for mares. To also to the genus Equus gehörendem Zebra found in the veterinary literature no evidence of ERU diseases.

Equine recurrent uveitis and human medicine

As a most likely immune-associated disease, the ERU shows similarities with various human autoimmune uveitis diseases for which a genetic background is suspected. These are, for example, Adamantiades-Behçet's disease , ocular sarcoid or Vogt-Koyanagi-Harada syndrome . Horses and humans show similarly altered immune responses that play a crucial role in the development of the disease.

Research into the molecular biological background of these similar diseases, both in veterinary and in human medicine, is currently focused on genes of the MHC class I and II complexes and the leukocyte antigen complex (see also Human Leukocyte Antigen ).

Findings from research into ERU could therefore help to better understand uveitis, which also occurs in humans and is partially immune-mediated.

literature

  • Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. In: Olof Dietz, Bernhard Huskamp: Handbuch Pferdepraxis . 3rd edition, Georg Thieme Verlag, Stuttgart 2005, ISBN 978-3-8304-1102-4 , pp. 775-786.
  • József Tóth, Josef Hollerrieder, Péter T. Sótonyi: Ophthalmology in horses: atlas and textbook. Schattauer Verlag for Medicine and Natural Sciences, Stuttgart 2010, ISBN 978-3-7945-2638-3 , pp. 180-186
  • Bernhard M. Spiess: Equine recurrent uveitis - the European viewpoint. Equine Veterinary Journal Volume 42, Issue 37, March 2010, pp. 50-56. doi: 10.1111 / j.2042-3306.2010.tb05635.x
  • Brian C. Gilger: Equine recurrent uveitis: The viewpoint from the USA. Equine Veterinary Journal Volume 42, Issue 37, March 2010, pp. 57-61. doi: 10.1111 / j.2042-3306.2010.tb05636.x
  • Brian C. Gilger, Tammy Miller Michau: Equine recurrent uveitis: new methods of management. The Veterinary Clinics of North America / Equine Practice, Volume 20, Issue 2, 2004, pp. 417-427. doi: 10.1016 / j.cveq.2004.04.010 PMID 15271431 (only abstract)
  • Linda Frellstedt: Equine recurrent uveitis: A clinical manifestation of leptospirosis. Equine Veterinary Education, Volume 21, Issue 10, 2009, pp. 546-552. doi: 10.2746 / 095777309X467853
  • Rudy A. Hartskeerl, Marga GA Goris, Siegfried Brem, P. Meyer, H. Kopp, Hartmut Gerhards, Bettina Wollanke: Classification of Leptospira from the Eyes of Horses Suffering from Recurrent Uveitis. Journal of Veterinary Medicine, Series B, Volume 51, Issue 3, pp. 110-115, April 2004. doi: 10.1111 / j.1439-0450.2004.00740.x
  • Florian Hofmeier: Equine Recurrent Uveitis - Pathogenesis Associated Factors in the Vitreous Body. Dissertation, LMU Munich: Faculty of Veterinary Medicine, 2010. available online
  • Maike Kulbrock, Ottmar Distl, Bernhard Ohnesorge: A Review of Candidate Genes for Development of Equine Recurrent Uveitis. Journal of Equine Veterinary Science 33, 2013, pp. 885-892. doi: 10.1016 / j.jevs.2013.01.005
  • Fernando Malalana, Amira Stylianides, Catherine McGowan: Equine recurrent uveitis: Human and equine perspectives. The Veterinary Journal Volume 206, Issue 1, October 2015, pp. 22-29. doi: 10.1016 / j.tvjl.2015.06.017
  • Eugen Fröhner: Forensic veterinary medicine. 4th edition, Schoetz Verlag, Berlin 1915 ( online , periodic eye inflammation, pp. 65–70)
  • D. Braun: The history of research and treatment of the "periodic eye inflammation" of the horse in German-speaking countries from 1750–1950. Equine medicine, Volume 11, Issue 1, 1995, pp. 43–49. Available online
  • Stefan Gesell: Therapy of the ERU. Horse mirror 01/2016. https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-0041-110002

Web links

Individual evidence
  1. ^ A b c Bernhard M. Spiess: Equine recurrent uveitis: the European viewpoint. P. 50
  2. ^ Brian C. Gilger: Equine recurrent uveitis: The viewpoint from the USA.
  3. ^ RE Halliwell, MT Hines: Studies on equine recurrent uveitis. I: Levels of immunoglobulin and albumin in the aqueous humor of horses with and without intraocular disease. Current Eye Research, 4 1985
  4. ↑ a b Bernhard Spiess: Equine recurrent uveitis. Swiss Veterinary Archives, 139, 1997
  5. ^ Brian C. Gilger, Tammy Miller Michau: Equine recurrent uveitis: new methods of management. P. 417
  6. ↑ Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 775
  7. ^ A b Jószef Tóth, Josef Hollerieder and Péter Sótonyi: Ophthalmology in horses. Textbook and atlas. P. 180
  8. ^ M. Nelson: Equine recurrent uveitis, a report of 68 horses in the United States and Canada. ERU Network 1995.
  9. ^ Brian C. Gilger, Tammy Miller Michau: Equine recurrent uveitis: new methods of management. P. 426
  10. ↑ a b eyevet.ch: Moon blindness / periodic eye inflammation / recurrent uveitis  ( page no longer available , search in web archives )  Info: The link was automatically marked as defective. Please check the link according to the instructions and then remove this notice.@1@ 2Template: Dead Link / www.eyevet.ch  
  11. ↑ a b c d D. Braun: The history of the research and treatment of the "periodic eye inflammation" of the horse in the German-speaking area from 1750-1950.
  12. ↑ C. W Ammons: Treatise on the Nature and Cure of Eye Inflammation in Horses. 1807 and F. Toggias: On the causes of blindness in horses. 1821.
  13. ↑ Eugen Fröhner: Forensic veterinary medicine. P. 4, 66.
  14. ^ Ordinance on the main defects and warranty periods in the cattle trade - full text at Wikisource.
  15. ↑ a b R. A. Hartskeel, MGA Goris, S. Brem, P. Meyer, H. Kopp, H. Gerhards, B. Wollanke: Classification of Leptospira from the Eyes of Horses Suffering from Recurrent Uveitis.
  16. ↑ a b c Bettina Wollanke: Equine recurrent uveitis (ERU) as intraocular leptospirosis. Habilitation thesis, Ludwig Maximilians University Munich, 2002
  17. ↑ Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 781
  18. ↑ Jószef Tóth, Josef Hollerieder and Péter Sótonyi: Ophthalmology in horses. Textbook and atlas. P. 180f.
  19. ↑ see exemplary studies by: Brian C. Gilger, Jacklyn H. Salmon, Na Y. Yi, Curtis A. Barden, Heather L. Chandler, Jennifer A. Wendt, Carmen MH Colitz: Role of bacteria in the pathogenesis of recurrent uveitis in horses from the southeastern United States. American Journal of Veterinary Research, October 2008, vol. 69, no. 10, doi: 10.2460 / ajvr.69.10.1329
  20. ↑ a b c d e Jószef Tóth, Josef Hollerieder and Péter Sótonyi: Ophthalmology for horses. Textbook and atlas. P. 181
  21. ↑ a b c Maike Kulbrock, Ottmar Distl, Bernhard Ohnesorge: A Review of Candidate Genes for Development of Equine Recurrent Uveitis.
  22. ↑ Jószef Tóth, Josef Hollerieder and Péter Sótonyi: Ophthalmology in horses. Textbook and atlas. P. 176
  23. ↑ Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 775f.
  24. ↑ a b Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 778
  25. ↑ Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 779
  26. ^ A b c Brian C. Gilger: Equine recurrent uveitis: The viewpoint from the USA. P. 57
  27. ↑ Jószef Tóth, Josef Hollerieder and Péter Sótonyi: Ophthalmology in horses. Textbook and atlas. P. 182
  28. ^ Brian C. Gilger: Equine recurrent uveitis: The viewpoint from the USA. P. 58
  29. ↑ a b Stefan Gesell: Therapy of the ERU . In: horses mirror . tape 19 , no. 01 , March 1, 2016, ISSN  1860-3203 , p. 26-33 , doi : 10.1055 / s-0041-110002 .
  30. ^ Brian C. Gilger, Tammy Miller Michau: Equine recurrent uveitis: new methods of management. P. 420
  31. ^ A b c d e Brian C. Gilger, Tammy Miller Michau: Equine recurrent uveitis: new methods of management. P. 421f.
  32. ^ A b c Brian C. Gilger, Tammy Miller Michau: Equine recurrent uveitis: new methods of management. P. 422
  33. ↑ Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 782
  34. ↑ Jószef Tóth, Josef Hollerieder and Péter Sótonyi: Ophthalmology in horses. Textbook and atlas. P. 185
  35. ^ A b Brian C. Gilger, Tammy Miller Michau: Equine recurrent uveitis: new methods of management. P. 423
  36. ^ Brian C. Gilger: Equine recurrent uveitis: The viewpoint from the USA. P. 60
  37. ↑ a b c d Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 784
  38. ^ Ludwig-Maximilians-Universität München, Clinic for Horses - Information on vitrectomy and ERU for pet owners, as of February 2013
  39. ^ Center for Equine Ophthalmology: Vitrectomy in a Horse. Dr. Stefan Gesell-May, October 23, 2016, accessed on October 23, 2016 .
  40. ↑ a b c Hartmut Gerhards, Bettina Wollanke: Equine recurrent uveitis. P. 785
  41. ^ Stud book regulations for the European donkey breed, p. 5
  42. ↑ Fernando Malalana, Amira Stylianides, Catherine McGowan: Equine recurrent uveitis: Human and equine perspectives.
  43. ↑ Florian Hofmeier: Equine recurrent uveitis - pathogenesis associated factors in the vitreous humor. P. 19 ff.