Treatment Of Noninfectious Posterior Segment Uveitis

Treatment Of Noninfectious Posterior Segment Uveitis

October 01, 2021

Ophthalmology News - “The word ophthalmos, “οφθαλμος”  from which the term ophthalmology is derived, appears often in Homer’s epic poetry: “Athena aimed the arrow towards the nose, near the ophthalmos [eye] and pierced the white teeth” [Il 5.291].”

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Uveitis is an important cause of vision loss worldwide and is the third leading cause of vision loss in developed countries. 

Uveitis is classified on the basis of the location of inflammation into anterior (iritis, iridocyclitis, and anterior cyclitis), intermediate (pars planitis, posterior cyclitis, and hyalitis), and posterior (focal, multifocal, or diffuse choroiditis, chorioretinitis, retinitis, and neuroretinitis).

Panuveitis involves the inflammation of the anterior chamber, vitreous, retina, and choroid. Anterior uveitis is the most commonly encountered entity, and posterior uveitis constitutes 15%–22% of all cases of uveitis.                             Οφθαλμός

Posterior uveitis is the most difficult to treat due to challenges encountered in delivering efficacious levels of therapeutic agents and can lead to visual morbidity.

Chronic noninfectious posterior segment uveitis refers to inflammation of the retina, choroid, vitreous, or optic nerve, and may result in permanent vision loss. Ophthalmology News

The inflammation can be constant, or characterized by periodic exacerbations on an underlying baseline of inflammation. Ophthalmology News.

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When a patient presents with ocular inflammation, the hallmark of uveitis, the ophthalmologist is faced with a series of decisions.                        Οφθαλμός   Ophthalmology News

The first and most critical challenge is to determine whether the condition is infectious or noninfectious, as that will indicate which treatment pathway is to be followed.

Once a patient has been diagnosed with noninfectious posterior uveitis, practitioners can choose between local and systemic treatments. If local therapy is selected, treatment may be topical or intravitreal: in either case, new medical options are available. Ophthalmology News.

Because of the complex nature of the condition and individual patient, it may be advisable in the course of either diagnosis or treatment for the ophthalmologist to consult the patient’s internist or, in some cases, rheumatologist.

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While e­ffective management of uveitis presents challenges, today’s treatment options are safer, more e­fficacious, and more streamlined than in the past and o­ffer the promise of enduring remissions from symptoms.  Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

Uveitis is a group of inflammatory diseases that can lead to severe vision loss if left untreated. The incidence of uveitis is estimated at between 17 and 52 cases per 100,000 per year, with a prevalence of 38 to 714 cases per 100,000. Ophthalmology News

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Uveitis may originate from diseases occurring locally in the eye or as an extension of systemic inflammatory disease; 24% to 55% of cases are considered idiopathic. Uveitis can involve inflammation not only of the uvea but also the lens, retina, optic nerve, and vitreous.

Additionally, uveitis can be infectious or noninfectious, acute or chronic, and can a­ ect the posterior segment, anterior segment, or both. Symptoms, which may include blurred vision, floaters, eye pain, redness, and light sensitivity, vary according to the type and site of inflammation. Ophthalmology News.

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Early and appropriate treatment of uveitis is critical: when incompletely treated, uveitis’ characteristic recurrent inflammation impairs patients’ functioning and quality of life and can lead to vision loss. Ophthalmology News

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Because uveitis can arise from any one of multiple causes and can vary in terms of the type and extent of tissue involvement, it often presents as a diagnostic and therapeutic challenge.

Inflammatory, infectious, and cancerous diseases of the eye often present with similar ocular and neurological features.   Ophthalmology News

Diagnosis and treatment of complex, chronic, or refractory cases, therefore, often require knowledge that crosses between internal medicine, infectious diseases, rheumatology, and immunology.

Posterior uveitis, in particular, is usually treated by retinal specialists, who are familiar with treatments and procedures for the posterior segment.

Because of the multifaceted nature of uveitis diagnosis and treatment, practitioners caring for patients with uveitis face a series of challenges: arriving at an accurate diagnosis, treating the acute phase of the disease, and preventing symptom recurrence. Ophthalmology News

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As a result, educating practitioners on the treatment and diagnosis of uveitis is critical. We will provide guidance for negotiating the noninfectious posterior uveitis pathway and discuss important technological advances that have been made in posterior segment drug delivery. Ophthalmology News.

DIAGNOSTIC CHALLENGES

Diagnosis is the first step in treating patients with uveitis. Practitioners undertake a series of steps and tests to determine if a patient has uveitis and, if so, which type. Ophthalmology News.

Classifying Uveitis

Uveitis is classified in two ways, anatomic and etiologic. Anatomic classification is the purview of the ophthalmologist, whereas etiologic classification may involve teamwork with other medical specialists. Ophthalmology News

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Anatomic classification: Ophthalmologists conduct clinical examinations to classify potential uveitis cases based on which tissues show inflammation.  Ophthalmology News

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When inflammation appears in the front of the eye, the condition is classified as anterior uveitis, which is also known as iritis. Inflammation in the back of the eye indicates posterior uveitis; if inflammation occurs throughout the eye, it is diagnosed as panuveitis. Ophthalmology News

To rule out panuveitis, the examining physician must ensure that observed anterior uveitis does not have a posterior component and vice versa. When uveitis occurs in the posterior segment, it commonly involves the retina and choroid.

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In the United States, posterior uveitis is the third most common form of uveitis after anterior and panuveitis, respectively. In patients ≥ 65 years of age, however, posterior uveitis is more prevalent than other forms of nonanterior inflammation, comprising 53% of nonanterior cases. Ophthalmic News

According to the Standardization of Uveitis Nomenclature (SUN) classification, posterior uveitis includes focal, multifocal or di­ use choroiditis, chorioretinitis, retinochoroiditis, retinitis, and neuroretinitis. Ophthalmology News

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Compared with anterior uveitis, posterior uveitis carries a greater morbidity and poorer prognosis. Vision threatening complications in patients with noninfectious posterior uveitis include macular edema, cataract, glaucoma, vitreous debris, and retinopathy. Ophthalmology News

Macular edema, which was reported in 8.3% of patients with noninfectious uveitis in a retrospective analysis of 334 patients from the Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS), is the most frequently encountered structural complication of uveitis that results in central visual impairment, followed by epiretinal membrane and glaucoma (6.3% and 4.2%, respectively).

Etiologic classification: The origin of a patient’s uveitis determines how it is best treated, and uveitis can stem from infectious or noninfectious causes. Because infectious and noninfectious uveitis can share many common clinical symptoms and signs, etiological diagnosis is challenging. Ophthalmic News

It is only when an infectious etiology is ruled out that the practitioner’s focus can move to treating inflammatory rather than infective mechanisms. Ophthalmology News

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Clinical Examination: One of the most critical steps in properly diagnosing and treating uveitis is the clinical examination.                    Οφθαλμολογικά Νέα

Clinical symptoms of anterior uveitis are a red, painful eye accompanied by anterior chamber cell and flare, posterior synechiae, and keratic precipitates. Posterior uveitis causes worsened vision and visual field changes, chorioretinal lesions, retinal whitening, and vascular sheathing.

Inflammation in the vitreous may impede visualization of the posterior segment, in which case a PCR assay on an anterior chamber specimen may be required. Ophthalmic News

Inflammation in the posterior segment may involve adjacent structures such as the retina, vitreous, optic nerve head, or retinal vessels, along with choroidal inflammation. Ophthalmology News

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The examining physician may, therefore, find it helpful to keep the following questions in mind throughout the investigative process: Is this inflammation choroiditis, retinitis, or retinochoroiditis?

Are the optic nerve head or the retinal vessels involved? Do the clinical features suggest any known infective or noninfective entity? Are there associated anterior segment inflammation, vitritis, or complications? Is the condition associated with other systemic features? Is it recurrent?

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If so, how has it responded to previous therapy? Finally, is it associated with an immunocompromised state? History: A detailed medical history will help to determine whether the patient may have an infectious condition.                          Οφθαλμολογικά Νέα

Ophthalmologists should ask about any prior inflammatory events or infections in the eye, such as herpes or varicella, as well as any known infectious diseases, such as tuberculosis or Lyme disease.

Practitioners should ask about high-risk sexual behavior, which could put the patient at risk for syphilis or human immunodeficiency virus. Additionally, exposure to pets or other animals might suggest toxoplasmosis or toxocaraiasis.

In a 2015 study by Bajwa et al, toxoplasmosis was the most common cause of posterior uveitis. Practitioners should ask about recent illnesses or hospitalizations. Lyme disease, syphilis, tuberculosis, and sarcoidosis all have significant systemic ramifications that can contribute to uveitis.

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In adolescents and adult patients, it is very important to exclude syphilis. The patient’s internist may be able to provide important background information that will help in the diagnosis. Ophthalmic News

Age range: Underlying conditions a­ ecting uveitis etiologies or severity may appear more or less commonly depending on patient age.                         Οφθαλμολογικά Νέα

For instance, younger patients are more likely to have juvenile rheumatoid arthritis, Behçet’s disease, or ankylosing spondylitis, whereas in older patients, it is important to rule out lymphoma or syphilis.

Laboratory tests: Additionally, ophthalmologists can order a battery of laboratory tests to determine whether uveitis is caused by bacteria, virus, fungus, or another source. A thorough workup for uveitis would include a complete blood count as well as sedimentation rate. Ophthalmic News

Other blood tests might include rheumatoid factor, antinuclear antibody to rule out rheumatoid arthritis, and angiotensin-converting enzyme for sarcoidosis. In younger patients with back pain, it would be helpful to test for HLA-B27 or a simple lumbo-sacral Xray to rule out ankylosing spondylitis.

If the patient has cats or dogs or has been exposed to other animals, the practitioner should test for toxoplasmosis or toxocaraiasis. A skin test, blood interferon-gamma release assay, or chest X-ray should be conducted to rule out tuberculosis. Ophthalmology News

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Additionally, imaging techniques such as fundus fluorescein angiography (FFA), indocyanine green angiography (ICG), ultrasonography (USG), and optical coherence tomography (OCT) may be used to shed light on the presence or nature of infection in the eye.   Ophthalmic News

Idiopathic uveitis: As has been noted, up to half of uveitis cases will, after careful workup, be classified as idiopathic. Ophthalmology News

However, it has been suggested that some “idiopathic” cases may reflect incomplete patient medical history or imperfect laboratory testing and may actually be uveitis secondary to sarcoidosis, tubulointerstitial nephritis, or ankylosing spondylitis. Ophthalmology News -

TREATMENT CHALLENGES

The first goal of treatment is to suppress the inflammation and improve the patient’s symptoms quickly. The second goal is to prevent recurrences and thereby prevent the damage to optical tissues that can lead to permanent vision loss.   Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

Local or systemic treatment: In deciding whether to use local or systemic treatment, it is important to consider whether the uveitis is unilateral, bilateral, or unilateral alternating. Ophthalmology News -

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In unilateral alternating disease, either eye may be a­ ected by an attack, but only one eye is a­ ected at a time, and the attacks are recurrent in nature. Local treatment is more likely to be used in unilateral uveitis.    Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

Topical steroids are typically the initial treatment for noninfectious uveitis. Topical steroids have the advantage of being relatively benign and easy to discontinue. They also don’t penetrate very far past the anterior chamber, which means that they will not make an infectious disease worse.

Because of their limited penetration, however, steroids have less e­fficacy in the posterior segment than other options, such as injections. Ophthalmology News     Ophthalmic News     Ophthalmology

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For that reason, patients with noninfectious, locally-treated posterior segment uveitis are likely to be started on intravitreal steroids, most often in the form of the dexamethasone intravitreal implant, due to its proven e­fficacy and safety.   Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

The dexamethasone intravitreal implant is e­ffective at high doses, but it has a short duration of efficacy. It peaks within two weeks of initiation, and the benefits last approximately 4 months.

Like other steroids, the dexamethasone intravitreal implant can raise IOP, but the elevations do not appear to be cumulative.  Οφθαλμολογικά Νέα

In cases where the uveitis is unilateral and patients continue to have recurrent flare-ups after initial therapy with an intravitreal steroid, the fluocinolone actetonide (FAc) intravitreal implant is often e­ effective as maintenance therapy. Ophthalmology News         Ophthalmic News     Ophthalmology

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Many practitioners will choose to start their patients with noninfectious uveitis on the Ophthalmic News dexamethasone intravitreal implant, and then, once the inflammation is controlled and any macular edema has resolved, they convert them to the FAc intravitreal implant, which is long-acting, even at low doses. Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

Systemic treatment options include systemic corticosteroids, biologics such as adalimumab and infliximab, or an immunosuppressive agent such as methotrexate. Ophthalmology News    Ophthalmic News

Patients with bilateral symptoms may be prescribed systemic corticosteroids when topical corticosteroids are insu­fficient, or when the patient has a systemic disease that also requires therapy.

Systemic therapy for noninfectious uveitis is highly e­ffective but also has a significant side e­ffect profile. Practitioners prescribing systemic therapy may wish to consult a rheumatologist, as these specialists have experience in dealing with the side e­ffect profile of these drugs. Ophthalmology News

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Because every patient is di­fferent, the systemic therapies need to be tailored to the patient’s circumstances and based on the etiology of their disease. Ophthalmology News     Ophthalmic News

Some patients may not be candidates for systemic therapy because they have contraindications to it, such as pregnancy, where the potential for drug teratogenicity must be taken into consideration; other patients may simply prefer local treatment. Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

Additional considerations common with systemic therapies for uveitis are insurance coverage and cost. Concerns with local treatments: With local therapies, the two most significant concerns are intraocular pressure (IOP) elevation and cataract.   Ophthalmic News

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A study investigating the frequency and degree of ocular hypertension associated with sequential injections of the dexamethasone intravitreal implant found that the frequency of mild (≥ 23 mmHg) and moderate (≥ 25 mmHg) ocular hypertension increases with repeated injections, but the frequency of severe ocular hypertension (≥ 30 mmHg) remains comparable regardless of the frequency of injections. Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

Therefore, if a patient does not have an IOP spike of above 30 mmHg after a single implant, it is unlikely that subsequent implants would cause such an IOP spike. Despite the therapeutic benefits of the dexamethasone implant, temporary IOP spikes have been described in 27% to 32% of patients.

The significance of these spikes in terms of long-term visual damage was assessed in a retrospective review of 306 charts of patients who received the dexamethasone implant for a variety of diagnoses, including posterior uveitis. Ophthalmology News      Ophthalmic News     Ophthalmology

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Eligible patients were divided into cross-sectional and prospective groups depending on the following criteria:                              Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

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Cross sectional: IOP spikes ≥ 22 mm Hg up to 16 weeks post-implant and OCT retinal nerve fiber layer (RNFL) imaging of both eyes performed ≥ 3 months after the IOP spike (N = 48) Ophthalmology News

Prospective: OCT RNFL imaging performed within one year prior to dexamethasone implantation, IOP spike ≥ 22 mmHg up to 16 weeks after DEX implant, and OCT RNFL imaging performed ≥ 3 months after the IOP spike (N = 21) Up to 48% of these patients had a prior history of glaucoma.

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In the cross-sectional group, IOP spikes ≥ 22 mmHg after dexamethasone implantation demonstrated no significant di­fference in average RNFL thickness when compared with the contralateral untreated eye regardless of treatment diagnosis, magnitude of IOP spike, or history of glaucoma. Ophthalmology News

Similarly, the prospective group also demonstrated no significant di­ erences in average RNFL thickness when comparing measurements before and at least 3 months after the IOP spike.

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This study showed that a temporary elevation of IOP after dexamethasone implantation does not appear to cause a meaningful change in RNFL thickness when treated with IOP-lowering drops, regardless of etiology or magnitude of IOP increase. Ophthalmology News      Ophthalmic News     Ophthalmology

Also, in this study, topical IOP-lowering drops seemed to be adequate in the management of temporary IOP spikes to prevent RNFL damage even in patients with a past ocular history of glaucoma. Ophthalmic News

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In younger patients, it may be preferable to use topical therapy because of the risk of cataracts with intravitreal steroids. Conversely, inflammation itself can potentially cause cataract formation, so it is worthwhile to involve these patients in a discussion of risks versus benefits. Ophthalmology News

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The concept of cataract surgery may be less daunting to patients older than 40 years, who are, in general, more likely to be concerned about IOP. Ophthalmology

Regardless of the patient’s age, it is critical to prevent recurrences of uveitis over time, because multiple recurrences can damage ocular structures and lead to visual decline. Ophthalmic News

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Further, the chronic macular edema associated with recurrent uveitis causes loss of retinal pigment epithelium, with deleterious consequences for visual acuity. The selection of appropriate therapy for a patient with noninfectious posterior uveitis must be as individualized as the diagnosis. Ophthalmic News

It may depend on the patient’s medical and optical history, the method or frequency of administration, contraindications to systemic or local therapies, and other circumstances, including patient preferences. Ophthalmology News

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For many adult uveitis patients, balancing their treatment with their work responsibilities is an important issue. There is potentially a place for subtenons injections, especially for patients who have cystoid macular edema, there may be a need for it. Ophthalmology News

The clinician must take all of these factors into consideration to best serve the patient’s needs while at the same time, providing safe, e­ffective, and durable relief of the symptoms of uveitis. Ophthalmic News

The Multicenter Uveitis Treatment Trial (MUST):

MUST compared the FAc 0.59 mg insert with systemic therapy (initially prednisone with the addition of an immunosuppressive agent if required) over a 7-year period in 255 patients. Ophthalmology News

After 2 years, there was little di­fference in best corrected visual acuity (BCVA) between the FAc implant and systemic treatment groups. Ophthalmology

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After 4.5 years, the implant provided better control of inflammation. However, after 7 years, visual outcomes in 180 patients were better in the systemic therapy treatment group, although patients receiving systemic therapy had a higher rate of antibiotic-treated infections. Ophthalmology News

At 7 years, 45% of eyes in the FAc implant group had undergone glaucoma surgery compared with 12% of eyes in the systemic therapy group. In phakic eyes, 90% of patients in the implant group had had cataract surgery versus 50% in the systemic therapy group. Ophthalmic News

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These results suggest that for the early years, local control works well. However, if patients have underlying conditions, such as systemic rheumatologic disease, it may be necessary eventually to convert them to systemic treatment. Ophthalmology News

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With respect to IOP elevations with FAc therapy in MUST, IOP data were available for 249 patients. Overall, 65% of patients assigned to the implant versus 24% of patients assigned to systemic therapy experienced an IOP elevation of at least 10 mmHg above the baseline measurement within the first 2 years of follow-up. Ophthalmology

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Over the 2 years, 69% of patients assigned to the implant received IOP-lowering therapy as compared to 26% in the systemic treatment arm (P < 0.001), and 32% of patients assigned to the implant versus 5% of patients assigned to systemic therapy received a surgical intervention (P < 0.001).                                  Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

For patients receiving implants, IOP elevations were common in the first year: 58% experienced an elevation of at least 10 mmHg. Incident IOP elevation of 10 mmHg or more occurred in 8 additional patients after 12 months in the implant group. Ophthalmology

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The median time from implant surgery to an IOP increase of at least 10 mmHg was 9 months in patients assigned to implants. In patients with bilateral implants, once an event occurred in one eye, the risk of an IOP elevation or of having IOP-lowering surgery was higher in the fellow eye.

Twenty-seven (23%) patients assigned to implant developed glaucoma, 9 of which developed it in both eyes. With the exception of 4 eyes in 4 patients, all cases of glaucoma observed were in eyes that received an implant regardless of the original treatment assignment. Ophthalmology

In general, IOP response to steroids is relatively predictable. The majority of IOP responders present relatively early, after the second or third injection. Those who are not steroid responders early on are unlikely to become steroid responders later. Οφθαλμός  Οφθαλμολογικά Νέα  όλοι βλέπουν τα μάτια του θεού  όλα βλέπουν τα μάτια

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Because of the potential for harm if left untreated, the MUST investigators recommended that all patients receiving the FAc implant should be evaluated for IOP at least every 6 weeks and possibly more frequently. Ophthalmology

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Patients with noninfectious posterior uveitis are likely to require multiple o­ffice visits and coordination with several providers. Practitioners will need to compile and interpret di­fferent pieces of information from a variety of sources. Ophthalmology

The challenge is to coordinate this information to create a treatment plan that is not only e­fficacious, but workable. Newer therapies and better understandings of how to work with them have greatly improved disease management and prognosis for these patients. Ophthalmology

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Witnessing such a Ptolemaic view of the universe, a masterfully combined design of Geometry, light, and cosmology!  Ophthalmology News -- Understanding at once that it is not by any human power or skill, but by the influence of Great Architect Of The Universe  that this site has been so wonderfully built.

Uveitis patients now have more e­ icacious, safer, and less expensive treatment options, which o­ er a greater potential for preserving vision, independence, and quality-of-life over the long term.

Ophthalmology News. - Transmutes all creation and our lives into something precious and sacred, to be loved, embraced, cherished and celebrated because the life we see and experience here is the emanation of the divine ground. Illumination Of The Great Architect of The Universe…

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