Affected individuals generally suffer from photophobia and decreased visual acuity, and may claim ocular pain [1]. They usually present with red eyes. Generally, hyperemia is most prominent in close proximity to the limbus. The severity of redness and ocular pain is highest in acute-onset AU, whereas chronic disease is associated with minimal redness and pain [2]. Pupils of the affected eyes are typically constricted and dilate to a lesser extent in response to light stimulation. Ocular discharge is not usually observed.

Some AU patients remain asymptomatic until complications arise. They don't present with characteristic "red eyes", but instead have "white eyes". This particularly applies to patients with juvenile idiopathic arthritis-related uveitis or Fuchs heterochromic iridocyclitis.

• Sepsis

  Conjunctival samples are useful for cytology, cultures, direct parasite observation and PCR Causes of Canine Anterior Uveitis Unknown-Idiopathic Trauma (accidental and surgical) Viral: Hepatitis, Distemper Bacterial: Corneal wounds, Bacterial sepsis [vin.com]

  Panuveitis caused by Klebsiella sepsis that arose from a urinary tract infection two weeks earlier. The patient had been treated and was feeling better when the eye became painful and red. A 2-mm hypopyon is present (arrow). Figure 4. [aafp.org]

  Some other systemic diseases (for example, Behçet’s disease, syphilis or systemic sepsis and metastatic endophthalmitis presenting with hypopyon uveitis) may be immediately life‐threatening and require emergency management. [onlinelibrary.wiley.com]

• Aphthous Stomatitis

  Other systemic features are keratoderma blenorrhagica, balanitis, and aphthous stomatitis. [21],[25] c) Inflammatory bowel disease: Crohn's disease, ulcerative colitis and Whipple's disease may present with acute recurrent iridocyclitis. [21],[25] d) [ijo.in]

• Tinnitus

  […] endemic Tubular interstitial nephritis Anterior Unknown Fever, arthralgias, rash, nephritis Urinalysis, renal function studies Ocular symptoms can precede renal disease Vogt-Koyanagi-Harada syndrome Posterior 100 Vitiligo, poliosis, alopecia, meningismus, tinnitus [aafp.org]

• Fracture

  Risk of thoracolumbar fractures doubled in victims of motor vehicle collisions with cervical spine fractures. J Trauma. 2006 Sep. 61(3):686-7. [Medline]. Duane TM, Dechert T, Wolfe LG, Aboutanos MB, Malhotra AK, Ivatury RR. [medscape.com]

  If the vertebrae fuse together, the spine loses its mobility, leaving the vertebrae brittle and vulnerable to fractures. Ankylosing spondylitis may also cause a curvature of the spine. [emedicinehealth.com]

  Fusion increases susceptibility to fracture, even resulting from small traumas. [scielo.br]

• Anterior Uveitis

  In one community-based study, anterior uveitis accounted for more than 90% of all cases of uveitis. [emedicine.medscape.com]

  Home Noninfectious anterior uveitis Noninfectious anterior uveitis: An inflammatory disease of the eye. Uveitis, in its various forms, is estimated to be responsible for 10% of the blindness in the United States. [aldeyra.com]

  Uveitis may be anterior, intermediate, posterior or panuveitis... [readbyqxmd.com]

• Photophobia

  Pupillary examination may reveal direct photophobia when the light is directed into the affected eye, as well as consensual photophobia when light is directed into the uninvolved eye; consensual photophobia is typical of iritis, whereas photophobia due [emedicine.medscape.com]

  Clinical features: Symptoms: pain due to ciliary spasm, red eye, photophobia, decreased vision and tearing Signs: Circumcorneal ciliary injection, irregular pupil or miosis Cells or flare in the aqueous and hypopyon within the anterior chamber are a sign [dro.hs.columbia.edu]

  […] autoimmune condition such as ankylosing spondylitis, juvenile rheumatoid arthritis, Reiter syndrome, sarcoidosis, herpes simplex, herpes zoster, or Behçet disease Delayed diagnosis and treatment may lead to irreversible vision loss Periocular pain and photophobia [kellogg.umich.edu]

  A 14-year-old girl was seen for pain, redness, and photophobia shortly after finishing a cycle of high-dose Ara-C. [ncbi.nlm.nih.gov]

• Blurred Vision

  Acute anterior uveitis presents as follows: [2] Pain, generally developing over a few hours or days except in cases of trauma Redness Photophobia Blurred vision Increased lacrimation Chronic anterior uveitis presents primarily as blurred vision and mild [emedicine.medscape.com]

  We report the case of a 13-year-old girl who consulted for blurred vision, pain, and redness in her left eye. Ophthalmologic examination revealed chronic, hypertensive, and non-granulomatous anterior uveitis. [ncbi.nlm.nih.gov]

  […] of calcific band keratopathy, cataract, or CME • Intermediate uveitis • symptoms of floaters and blurred vision. • Floaters result from the shadows cast by vitreous cells and snowballs on the retina. • Blurred vision may be caused by CME or vitreous [slideshare.net]

• Eye Pain

  This report describes 2 patients who experienced eye pain, photophobia, redness, and edema after undergoing alexandrite (755 nm) laser epilation of the eyebrow area while not wearing protective eyewear or a corneal shield. [ncbi.nlm.nih.gov]

  Anterior uveitis is usually treated by using two different medicated eye drops. One serves to reduce the eye pain associated with the pupil changing size. The second reduces the inflammation. [optom.on.ca]

  The symptoms of anterior uveitis may include eye redness, light sensitivity (photophobia), tearing, eye pain, and blurred vision. Discharge from the eyes is uncommon. [emedicinehealth.com]

  • 38 year old male complained of right eye pain and redness for 5 days duration. [slideshare.net]

  The symptoms of Anterior uveitis include light sensitivity, throbbing eye pain, and blurred vision. The eye will look very red and inflamed and some patients need to wear sunglasses to help with the light sensitivity. [opto.ca]

• Miosis

  Clinical features: Symptoms: pain due to ciliary spasm, red eye, photophobia, decreased vision and tearing Signs: Circumcorneal ciliary injection, irregular pupil or miosis Cells or flare in the aqueous and hypopyon within the anterior chamber are a sign [dro.hs.columbia.edu]

  External examination Miosis Endothelial dusting Aqueous flare and cells 20. [slideshare.net]

  Pupillary miosis is common. Slit-lamp examination This is the most important aspect of the examination. Examine the cornea via direct illumination with a broad beam at a 30°-40° angle between the viewing microscope and the light source. [emedicine.medscape.com]

  The constriction of the pupil’s sphincter causes its contraction (miosis), while in serious cases, the inflammatory elements accumulate at the lower part of the anterior chamber forming hypopyon. [athenseyehospital.gr]

• Dizziness

  Dizziness: Feelings of dizziness may occur, especially when getting up from a sitting or lying position. Weight gain: Some of the second generation drugs are thought to affect people’s sense of having had enough to eat. They can also be sedating. [camh.ca]

  The drug has been known to cause dizziness, arrhythmia (irregular heartbeat), and postural hypertension (a drop in blood pressure when standing). [verywellmind.com]

  The most common side effects of quetiapine are somnolence, orthostatic hypotension, and dizziness. Ziprasidone has almost no weight gain but can cause prolongation of QTc. [ncbi.nlm.nih.gov]

  Side effects often associated with TCAs and MAOIs include drowsiness, weight gain, dry mouth, constipation, blurred vision, dizziness and sexual dysfunction. Because of these side effects, doctors will usually prescribe a newer antidepressant first. [heretohelp.bc.ca]

AU is diagnosed clinically. But while certain clinical features may be recognized easily during general and ophthalmological examinations, attention to detail is required when it comes to associating the uveal inflammation with an underlying disease. In this context, both anamnestic and clinical data have to be evaluated [3]:

• While unilateral AU most likely indicates a viral infection, mycobacterial infections more frequently result in bilateral eye involvement. HLA-B27 positive uveitis may alternately affect both eyes.
• If keratic precipitates are detected during slit-lamp examination, special attention should be paid to their form, size, and distribution [4]. Fine and spiculated precipitates covering the entire cornea point at Fuchs heterochromic iridocyclitis, but precipitates of medium or large size are more commonly related to viral and mycobacterial infections, respectively. Scleritis may point at AU of autoimmune or infectious origin.
• Iris heterochromia is to be expected in cases of Fuchs heterochromic iridocyclitis, while iris transillumination has been related to viral AU. The presence of posterior synechiae essentially rules out Fuchs heterochromic iridocyclitis.
• Hyphema and hypopyon may be diagnosed in those suffering from bacterial or viral AU, autoimmune disease, or uveitis-glaucoma-hyphema syndrome. The presence of aqueous cells in the anterior chamber is most commonly observed in case of viral infections.
• Ocular hypertension is often related to infectious AU. However, it may also be noted in those who have developed AU due to steroid treatment or lens implantation. Significant reductions of intraocular pressure are characteristic of HLA-B27 positive uveitis.

Once all these aspects have been considered, a tentative diagnosis as to the etiology of AU can be made and targeted studies can be carried out to confirm or refute the initial suspicion, e.g., anterior chamber paracentesis and subsequent polymerase chain reaction, but also laboratory analyses of blood samples and serological tests. There's also a wide range of imaging techniques, such as optical coherence tomography, sonography, microscopy, and angiography, that may be used to assess structure and function of ocular tissues [4].

Both local and systemic therapy may be indicated to treat AU. Systemic therapy is preferred if patients don't respond to local treatment, if they experience intolerable side effects, and if they present with extraocular symptoms [3].

Infectious AU requires antiviral or antibiotic therapy. There are no guidelines on treatment regimens, but valacyclovir, valganciclovir, and ganciclovir have been recommended to fight infections with herpes virus, varicella-zoster virus, or cytomegalovirus. Tuberculous uveitis is likely to improve with isoniazid, rifampicin, pyrazinamide, and ethambutol, while penicillin G is efficient against Treponema pallidum. β-lactam antibiotics less susceptible to β-lactamases have to be applied to treat Lyme disease with AU.

The local application of eye drops and ointment containing corticosteroids is the treatment of choice in case of non-infectious AU. Because steroid therapy may aggravate infectious diseases, it is important to rule out the presence of viral or bacterial pathogens in advance. Initially, eye drops are instilled hourly during the day and ointments are used at night. The frequency of installation is subsequently adjusted depending on severity and progression of the disease. If the application of drops and ointments doesn't yield the desired results, steroids may be injected subconjunctivally. Intraocular steroid depots may be considered if posterior segment complications arise.

Steroids may also be required to treat chronic AU. However, doses should be reduced as much as possible to avoid the side effects of long-term steroid therapy. In recent years, monoclonal antibodies against tumor necrosis factor-α have increasingly been used to replace steroids in immunosuppressive therapies [5].

As a supportive measure, cycloplegics may be administered to patients suffering from either infectious or non-infectious AU. They serve a triple purpose: They relieve pain by immobilizing the iris, prevent the formation of synechiae, and reduce protein leakage by stabilizing the blood-aqueous barrier [6].

While all cases of AU should be treated as potentially sight-threatening, particularly high complication rates, a tendency for chronicity and long-term loss of visual acuity have been observed in children [7]. In both pediatric and adult patients, AU may entail distinct complications: Posterior segment complications such as optic disc or macula edema may occur. Furthermore, ocular hypertension may become chronic and may cause glaucoma. Other complications arise from prolonged steroid therapy, namely cataracts. Treatment of those complications bears the risk of rebound inflammatory responses and recurrent AU, and this especially applies to surgical interventions. Recurrent AU considerably worsens the prognosis for vision.

AU may be observed in patients suffering from distinct diseases, both infectious and non-infectious ones. The most common forms of AU are HLA-B27 positive uveitis, possibly of autoimmune origin, Fuchs heterochromic iridocyclitis, an entity of as-of-yet unknown etiology, and herpetic uveitis, caused by herpes virus strains [8]. Considering their heterogeneous etiologies, these three examples are well representative of the complex condition called AU.

AU is more frequently diagnosed in patients with (presumably) autoimmune comorbidities like Behçet disease, sarcoidosis, juvenile idiopathic arthritis, inflammatory bowel disease, and ulcerative colitis [3]. It may also be associated with multiple sclerosis. With regards to infectious causes, AU due to varicella-zoster virus infection or cytomegalovirus infection shall be named first. Posner-Schlossman syndrome has been related to cytomegalovirus infection. It may be considered an own entity, but is occasionally referred to as the acute form of cytomegalovirus AU [9]. Patients suffering from tuberculosis or leprosy, Lyme disease, leptospirosis or syphilis may develop AU [10] [11] as well as those infected with Toxoplasma gondii [12]. Finally, uveitis-glaucoma-hyphema syndrome shall be mentioned to illustrate the necessity to consider iatrogenic causes in AU patients.

Despite numerous studies on possible causes of AU, it is not always possible to identify the underlying condition. Indeed, more than half of all cases are still considered to be idiopathic [7] [13].

While AU is the most common form of uveitis, an inflammation of the uvea is only occasionally seen in clinical practice [13]. The overall incidence of uveitis has been estimated to 17 to 52 per 100,000 people per year, and the prevalence ranges between 38 and 714 per 100,000 inhabitants. With regards to individual causes of AU, incidence and prevalence vary greatly between industrialized nations and the developing world. For instance, infectious AU accounts for one in three cases in Africa and South America, with Toxoplasma gondii being the most common trigger. By contrast, infectious AU is rare in developed countries [7]. It should be kept in mind, though, that these data don't reflect all those idiopathic cases that cannot be related to any primary disorder.

Both men and women may develop AU. And while most patients are adults, children may suffer from AU, too. The most common non-infectious form of AU in pediatric patients is juvenile idiopathic arthritis-related AU. In general, the risk of developing AU due to autoimmune disorders increases with age [7]. All AU patients are potentially at risk of losing their vision and uveitis accounts for about 10% of cases of legal blindness in the United States [13]. In the developing world, this number may rise to 25% [7].

Pathophysiological processes underlying the development of AU are very heterogeneous. However, all forms of AU are associated with a breach in the blood-aqueous barrier. Only upon the breakdown of this barrier, white blood cells can enter the anterior chamber and surrounding tissues. While neutrophils typically dominate this process in case of acute AU, mononuclear cells play a major role in chronic disease. At the same time, protein extravasates from leaky vessels to the site of inflammation. Precipitates that may later be detected during the ophthalmological examination are aggregates of cell debris, inflammatory cells, and extravasated protein.

Measures to prevent infectious AU coincide with those generally recommended to reduce the personal risk of infection. Unfortunately, the etiology of most of those systemic diseases that may underlie AU is still poorly understood. Therefore, no recommendations can be given to prevent these forms of AU. This applies even more so to idiopathic AU.

In patients with chronic recurrent AU, relapses may eventually be prevented by continuous immunosuppressive therapy.

The term "uveitis" refers to an inflammation of the uvea, i.e., of the middle layer of the wall of the eye. Uveitides are categorized according to the primary anatomical location of inflammation: The uvea consists of the iris, the ciliary body, and the choroid, and AU is diagnosed when the iris and/or the ciliary body are affected. It has been estimated that AU accounts for 50 to 90% of all cases of uveitis [13]. Of note, other forms of uveitis are intermediate uveitis (pars planitis and cyclitis), posterior uveitis (choroiditis), and panuveitis (inflammation of all parts of the uvea). In any case, the inflammation may spread to adjacent ocular or extraocular tissues.

Uveitides are of highly heterogeneous etiology. Anamnestic data and clinical findings are most important to support a suspicion as to the causes of an individual case of AU. In this context, disease onset and progression, laterality, the involvement of certain ocular tissues, and extraocular symptoms have to be considered. To reliably assess the inflammatory process within the eye, a thorough ophthalmological examination is required. In that regard, the patient's visual acuity should be evaluated, and slit-lamp examination and fundoscopy should be performed. Imaging techniques may be required to examine ocular structures that cannot be viewed or gauged otherwise [2].

Depending on the causes of AU, treatment comprises antiviral or antibiotic agents, corticosteroids and other immunosuppressive compounds, and cycloplegics.

The eye is surrounded by a wall made of three layers, namely the fibrous sclera, the highly vascularized uvea, and the retina, which carries photoreceptors and nerve cells. An inflammation of the middle layer, the uvea, is called uveitis. Because the uvea comprises distinct anatomical structures, uveitides are further differentiated. An anterior uveitis (AU) is diagnosed if the inflammation arises from the anterior parts of the uvea, which are the iris and ciliary body. Still, the inflammation may spread to adjoining tissues.

An AU may have many causes. On the one hand, AU may be a symptom of infection. Viruses, bacteria, but also parasites may provoke AU. Herpes virus strains, varicella-zoster virus and cytomegalovirus, mycobacteria, and Toxoplasma spp. shall be named exemplarily to illustrate the diversity of pathogens that may trigger this type of inflammation. On the other hand, systemic disorders of autoimmune or as-of-yet unknown origin may also cause AU. With regards to children, AU is mostly observed in patients suffering from juvenile idiopathic arthritis. But adults suffering from sarcoidosis, inflammatory bowel disease, or ulcerative colitis, among others, are also prone to develop AU.

Diagnosis of AU requires thorough ophthalmological and general examinations. Only if detailed information regarding the onset and progression of the disease, the involvement of determined ocular structures, and the presence of extraocular symptoms is obtained, a tentative diagnosis as to the causes of AU can be made. In order to provide an adequate therapy, it is important to identify the cause of AU. Unfortunately, this cannot be achieved in all cases, and many patients are treated empirically. Close follow-ups should be ensured to assess the patient's response to therapy and to prevent long-term loss of visual acuity and blindness.

1. Mercieca K, Jones NP. Treatment of acute anterior uveitis in the community, as seen in an emergency eye centre. A lesson for the general practitioner? Eur J Gen Pract. 2012; 18(1):26-29.
2. Kestelyn PG. An eye on inflammatory eye disease. Acta Clin Belg. 2005; 60(5):270-275.
3. Gueudry J, Muraine M. Anterior uveitis. J Fr Ophtalmol. 2017.
4. Siak J, Mahendradas P, Chee SP. Multimodal Imaging in Anterior Uveitis. Ocul Immunol Inflamm. 2017; 25(3):434-446.
5. Lerman MA, Rabinovich CE. The Future Is Now: Biologics for Non-Infectious Pediatric Anterior Uveitis. Paediatr Drugs. 2015; 17(4):283-301.
6. Agrawal RV, Murthy S, Sangwan V, Biswas J. Current approach in diagnosis and management of anterior uveitis. Indian J Ophthalmol. 2010; 58(1):11-19.
7. Tsirouki T, Dastiridou A, Symeonidis C, et al. A Focus on the Epidemiology of Uveitis. Ocul Immunol Inflamm. 2016:1-15.
8. Miserocchi E, Fogliato G, Modorati G, Bandello F. Review on the worldwide epidemiology of uveitis. Eur J Ophthalmol. 2013; 23(5):705-717.
9. Chan NS, Chee SP, Caspers L, Bodaghi B. Review for Disease of the Year: Clinic of Cytomegalovirus-Induced Anterior Uveitis. Ocul Immunol Inflamm. 2017:1-9.
10. Sahin O, Ziaei A. Clinical and laboratory characteristics of ocular syphilis, co-infection, and therapy response. Clin Ophthalmol. 2016; 10:13-28.
11. Shetty SB, Devulapally SH, Murali S, Walinjkar JA, Biswas J. Tuberculous uveitis presenting as pigmented hypopyon - A case report. Am J Ophthalmol Case Rep. 2017; 7:1-3.
12. Massa HF, Gatzioufas Z, Mangioris G, Panos GD. Choroidoretinal granuloma in a young female patient. BMJ Case Rep. 2014; 2014.
13. Thorne JE, Suhler E, Skup M, et al. Prevalence of Noninfectious Uveitis in the United States: A Claims-Based Analysis. JAMA Ophthalmol. 2016; 134(11):1237-1245.