Post-op care Local: steroids, antibiotics lubricant eye drops systemic: control systemic disease
Scleral graft evaluation
within 4 weeks
Outcome: low rejection rate ( low living cells,denature protein) high necrosis rate particularly ( systemic RIA disease: vessel) precipitated immune complex; IMT is necessary)
How to manage specimens?
One third of tissue: infection survey
homogenized for smears, cultures, and PCR.
middle third of tissue: pathology survey
PAS stain, acid fast stain; HE stain ( granuloma)
( remained tissue: immunology stain for virus).
Remaining third: depend condition
Scleritis under systemic and topical steroid treatment
Careful exams and prompt treatment is necessary in the manage od scleritis
Thanks for your attention
Evaluation of specimens
Patients underwent an epibulbar biopsy (6 scleroconjunctival and 3 conjunctival) for evaluation of the presence of herpetic antigen within the tissues. The latter were fixed in Karnovsky solution or 10% buffered formalin and were embedded in plastic or paraffin, respectively. Tissue sections were stained with hematoxylin and eosin and were examined by light microscopy to assess any distinguishing histologic criteria. When granulomas were identified, a panel of special stains was used that included periodic acid–Schiff, Grocott methenamine silver, Ziel-Nielsen, Fite, and Brown-Hopps. A portion of the tissue was snap frozen, was embedded in Optimal Cutting Temperature medium (Tissue-Tek; Sakura Finetek, Torrance, California, USA), and was cut into 4-μm sections using a cryostat for immunofluorescent probing.
Evaluation of specimens
Immunofluorescence studies were performed on the patient specimens using standardized protocols. The specificity of the antibodies used in the immunofluorescence technique was confirmed using blocking antibodies: goat serum (Biodesign International, Saco, Maine, USA) for HSV and mouse serum (Biodesign International) for varicella zoster virus (VZV). Fluorescein isothiocyanate-conjugated goat antihuman HSV-1 immunoglobulin G (Biodesign International) was added to the patient's specimen to test for the presence of HSV antigen. This antibody is polyclonal and cross-reacts with HSV-2. Its relative specificity for the subtypes has not been quantified, and therefore it cannot reliably distinguish between HSV-1 and HSV-2. For VZV, the primary antibody used was mouse antihuman VZV monoclonal antibody (Biodesign International). The secondary antibody added was fluorescein isothiocyanate-conjugated goat antimouse immunoglobulin G (Biodesign International). The tissue was examined under an immunofluorescent microscope (Olympus BX-51; Olympus America Inc, Center Valley, Pennsylvania, USA). Normal human conjunctiva and sclera were used as negative controls.
Because corneoscleral grafts performed in the active phase of infection often result in necrosis, sloughing, or rejection, and because topical and subconjunctival antibiotics frequently fail to control infection, our greatest success in these cases has come from subpalpebral irrigation with broad-spectrum antibiotics before a corneoscleral graft. A scleral protection shell is placed over the eye, and 3 mL of 2% lidocaine with epinephrine is injected into the upper eyelid. An 18-gauge spinal needle is passed into the superior fornix to emerge through the skin of the upper eyelid. A 20-gauge spinal needle is then passed through the hub of a butterfly catheter to emerge from the distal end of the cut tube. The 20-gauge needle is inserted into the lumen of the 18-gauge needle, and both are pulled through the superior fornix as a guide for the tube. The needles are removed, and the end of the tube is tied into a knot and secured with a single 10-0 nylon suture to prevent unraveling. The knot is pulled into the fornix, and irrigation is initiated, typically with tobramycin (100 mg/liter), using an IV pump at 20 mL/min with maximum backpressure. This is continued for approximately 1 week until the infection becomes inactive and the patient can be switched to topical fortified tobramycin. Our recent experience with this technique has been promising: we have been able to control the inflammation in the eyes of several patients at the Los Angeles County Medical Center.
A step-ladder approach typically is used in the treatment of scleritis. The first-line therapy in treating non-necrotizing scleritis that is not caused by an infection is an NSAID. Two types of NSAIDs have been shown to be effective: flurbiprofen, 100 mg three times daily, and indomethacin, 25 to 50 mg three times daily  and . If one NSAID does not relieve the pain and inflammation, another may be tried.
Systemic glucocorticoids are used in three general settings: (1) when NSAIDs prove ineffective, (2) in cases of necrotizing anterior scleritis, and (3) in cases of posterior scleritis. The usual starting dose is 1 mg/kg/d (maximum of 60 mg/daily) followed by a tapering schedule based on clinical response. Table 3 describes the typical tapering schedule used in the authors' clinic. In patients whose disease appears particularly aggressive, pulse methylprednisolone can be administered intravenously at a dose of 1 g/d for 3 days, followed by the initiation of prednisone, 60 mg/d. The role of depot glucocorticoid treatment is controversial given the potential risk for scleral perforation with this therapy ,  and .
Possible second-line agents for scleritis include calcineurin inhibitors (cyclosporine or tacrolimus), infliximab, or rituximab , , ,  and ; however, none of these agents has been studied rigorously to date. In some cases of necrotizing anterior scleritis or scleromalacia perforans, surgical therapy is required to address extensive scleral thinning and avoid globe rupture. Scleral grafting surgery may be performed with donor sclera, periosteum, or fascia lata. Simultaneous efforts to control the underlying inflammation with medical therapy are essential when surgery is required.
The treatment of scleritis with immunosuppressive medications is fraught with the potential for treatment-related morbidity and mortality. Patients on high-dose glucocorticoids and other immunosuppressive agents require careful monitoring with frequent clinic visits and blood work. Patients on cyclophosphamide should have a complete blood count checked not less often than every 2 weeks. Prophylaxis against Pneumocystis carinii (jiroveci) pneumonia (PCP) is also critical, particularly when the combination of glucocorticoids and another immunosuppressive agent is used. One common approach to PCP prophylaxis is to use trimethoprim-sulfamethoxazole (one single-strength tablet daily). Evaluation for and prophylaxis against glucocorticoid-induced bone loss must also be considered.
Anterior scleritis treatment Patients with necrotizing anterior scleritis and those with nonnecrotizing anterior scleritis who do not respond to NSAIDs are started on oral prednisone at 1 mg/kg/d. This dose is continued until the scleritis is quiet for 1 month. The prednisone is then slowly tapered over a few months, depending largely on how well it was tolerated by the patient. Typically, if the patient do
The patient was referred to an oncologist for further evaluation. Chest radiograph was normal. Blood analysis showed hepatic alterations and neutropenia and a blood culture was positive for P. aeruginosa. With the diagnosis of P. aeruginosa sepsis, the patient was hospit
Patient 6 developed graft dehiscence in the postoperative period. In this particular case, graft was covered with amniotic membrane that retracted within 4 days leaving the sclera bare and predisposing the patient to further occurrence of this type. Scleral graft does not contain epithelium and survival is jeopardized on avascular surfaces, so a cover of conjunctival flap is necessary to prevent its necrosis and sloughing. If the adjacent conjunctiva cannot be mobilized, either a free conjunctival flap from the other eye or AMG may be considered.
Noting these characteristics of amniotic membrane and preserved homologous sclera, we performed preserved scleral patch grafts with AMT in patients who had scleromalacia with impending perforation. This surgical method resulted in fast reepithelialization and stable ocular conditions in all patients but one. In case 3, reepithelialization was delayed for 2 weeks after preserved scleral graft with AMT, so that antibiotics and serum therapy were necessary. Complete reepithelialization of the ocular surface was achieved 6 weeks after surgery with no evidence of microbial infection.
Scleral graft has many intrinsic advantages in this scenario as it is readily available from donor eyes, can be easily preserved for months and is strong, flexible, and easy to handle. Sclera has a natural curvature allowing it to neatly blend with host sclera. However, the biggest advantage is that it is avascular and is well tolerated with little inflammatory reaction. On the other hand, failure of scleral homografts has been reported owing to lack of vascularization with resultant necrosis and sloughing.2 In this communication, we report our experience with the use of scleral patch grafts.
Sclera: avascular tissue supplied by the vascular coats on episcleral choroidal side
Episclera: two vascular layers superficial and deep.
Choroidal: grooves caused by the passage of ciliary vessels
Communicate at the root of the iris
Why reddness 4 3 5 2
Systemic disorder:30- 57%
Infectious: 5% to 10%(biopsy)
Find underlying disease tertiary health center
image Autoimmune disease routine
Biopsy (Infectious, Masquerade)
Tropical Corticosteroids: failure rate 50%
NSAID: failure rate 8%
poor response to necrotizing scleritis
immunosuppression in visual-threatening cases
(MTX, cyclosporine, TNF blocker)
Adhesive: fibrin glue, Cyanoacrylate
Patching with autologous or homologous sclera, amniotic memb cartilage, fascia lata, periosteum, dermis, aortic tissue, dura mater, Gore-Tex (synthetic)
There is a vascular plexus of vessels within the conjunctiva and two vascular layers within the episclera, superficial and deep. The sclera itself is avascular, and, therefore, highly dependent on the vascular coats on either side. Anteriorly, the episclera has a rich blood supply from the anterior ciliary arteries, which form a rich plexus deep to the conjunctiva. These vessels form extensive collateral arterial anastomoses with the posterior ciliary arteries at the root of the iris and are normally inconspicuous but become visibly congested in the presence of inflammation.116
Approximately, 5–10% of cases of anterior scleritis are infectious , which includes viruses, bacteria, fungi, and parasites. Infectious scleritis is uncommon in the absence of infectious keratitis . Among the causes of infectious scleritis, herpes zoster virus is believed to be the most common pathogen. Pseudomonas aeruginosa is most commonly seen in cases of postsurgical scleritis. Fungal scleritis is a rare cause of scleritis and is often undiagnosed for months .
The differential diagnosis between peripheral ulcerative keratitis (PUK), associated with systemic vasculitides and collagen diseases (Wegener’s granulomatosis, polyarteritis nodosa and rheumatoid arthritis are the most common) [2, 3, 5, 22], and Mooren’s
ulcer is of decisive importance for the treatment of the corneal lesions, because in cases with Mooren’s ulcer the topical treatment, either medical or surgical, may arrest the progression of the disease. On the other hand, in cases with corneal ulcers associated
with a systemic vasculitis, the coverage of the patients with systemic immunosuppressive drugs along with (or without) systemic corticosteroids is necessary [2,3, 5, 23, 24], otherwise the therapeutic approach is inefﬁcient.
In conclusion the response of Mooren’s ulcer to the
therapeutic damage (excision and/ or cryoapplication)
of the conjunctiva is explained by the observation that
the conjunctiva adjacent to the ulcer is the pool of in-
ﬂ ammatory cells, collagenases and components of the
immune system, which induce the corneal lesions .
Therefore, by excising conjunctiva the melting process
is halted and thus there is the appropriate time for the
recovery of corneal lesions, resulting in decrease of
irregular astigmatism and visual acuity improvement
If an immunofluorescence assay is positive in either a cytoplasmic or perinuclear pattern (ie, C-ANCA or P-ANCA), then confirmation of the presence of the type of ANCA associated with is important, through enzyme immunoassays for antibodies to proteinase-3 or myeloperoxidase.
； Laboratory evaluation typically included a chest x-ray, fluorescent treponemal antibody absorption (for syphilis), urine analysis, serum chemistries (for renal disease), and, after 1987, the antineutrophil cytoplasmic antibody (ANCA) test. Both cytoplasmic ANCA (c-ANCA) testing and perinuclear ANCA (p-ANCA) testing were performed by immunofluorescence. In the appropriate patient, additional testing included rheumatoid factor, antinuclear antibody, HLA-B27, and Lyme antibody testing.
If an undiagnosed systemic disease was suspected, the patient was referred for appropriate rheumatological or gastrointestinal evaluation.
Diagnosis of vasculitis disease
the American College of Rheumatology criteria as guidelines.
Systemic vasculitis was categorized using the 1994 Chapel Hill Consensus Conference criteria.  The charts of all patients who were diagnosed with systemic vasculitis before 1994 were rereviewed to ensure that they met the newer diagnostic criteria, and only patients who met the 1994 Chapel Hill Consensus Conference criteria were considered to have systemic vasculitis. For any patient with an uncertain diagnosis on review, the medical record was reviewed by a rheumatologist, and a diagnosis was assigned.
Diagnosis of infectious disease
Herpes zoster ophthalmicus was diagnosed based on the characteristic clinical picture of a vesicular rash on the face in the area of the distribution of cranial nerve V. If the patient had a history of herpes zoster ophthalmicus, confirmation from the medical record or referring physicians was sought. Herpes simplex infection was diagnosed based on the characteristic clinical picture of a dendritic epithelial keratitis or stromal keratitis with a history of a dendritic epithelial keratitis. The diagnoses of syphilis and Lyme disease were based on the positive serologic testing for each infection, accompanied by a response to appropriate antibiotic therapy.
Why Classification Less ( F; 66Y/O) associated with systemic illness Necrotizing anterior scleritis immunosuppressive drugs (17%). Rare oral glucocorticoids (83%) Posterior scleritis Most cases respond to mild therapies 20-40 % NSAID(+) Steroid Nodular anterior scleritis Most cases respond to mild therapies 50 % NSAID(+) Steroid Diffuse anterior scleritis Prognosis Incident Treatment
* The diffuse and nodular subtypes of anterior scleritis (picture 1 and picture 2) have a reasonable likelihood of responding to NSAIDs alone. If the clinician's sense is that a more aggressive approach is required from the outset or if NSAIDs fail to control the scleral inflammation, most of these patients respond to high-dose prednisone. (See 'Glucocorticoids' below.)
* Necrotizing anterior scleritis or posterior scleritis (picture 3 and picture 4) are more likely to be associated with permanent ocular complications and should be treated aggressively. Most cases require cyclophosphamide as well as high-dose glucocorticoids.
Treatment 4 steroid
Tapering regimen — There is no standard tapering regimen for scleritis, but regimens similar to the one outlined below are often used. Assuming that a patient begins prednisone at 60 mg/day and remains on this dose for four weeks, the following taper will require a total of 24 weeks to reach a daily dose of 5 mg:
* The prednisone dose is tapered by 10 mg each week until a dose of 40 mg/day is reached.
* After one week on 40 mg/day, the prednisone dose is tapered by 5 mg each week until the dose reaches 20 mg/day.
* After one week on 20 mg/day, the prednisone dose is tapered by 2.5 mg each week until the dose reaches 10 mg/day.
* After one week on 10 mg/day, the prednisone dose is tapered by 1 mg every two weeks until the dose reaches 5 mg/day.
The patient should be monitored carefully during the tapering period, watching for signs of recurrent scleritis or the development of inflammatory disease in other organ systems. Sometimes what appears at presentation to be idiopathic scleritis turns out to be the harbinger of a multiorgan system disease.
Continuation of the prednisone taper can be considered if the patient has achieved and maintained good disease control. Tapering off prednisone completely should not proceed faster than 1 mg/day decreases every two weeks. Deviations from this regimen are often necessary if patients develop glucocorticoid myopathy or experience disease flares.
Azathioprine — Before beginning azathioprine, patients should be screened for thiopurine methyltransferase (TPMT) deficiencies. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Pharmacology'.)
The initial dose of azathioprine is 50 mg/day. If this dose is tolerated well at one week, the daily dose can be increased over several weeks to the range of 1.5 to 3 mg/kg per day. Most clinicians do not prescribe more than 200 mg/day, even for large individuals.
* Methotrexate — The initial dose is usually 15 mg/week, with increases in dose every week of 5 mg/week up to 25 mg/week.
* Mycophenolate mofetil — The typical dose of mycophenolate mofetil 1.0 to 1.5 g PO twice daily.
Folic Acid 5mg( 葉酸 )
Scleritis sometimes occurs in an isolated fashion, without evidence of inflammation in other organs. However, in up to 50 percent of patients, scleritis is associated with an underlying systemic illness such as rheumatoid arthritis or Wegener's granulomatosis . Two-thirds of patients with scleritis require high-dose glucocorticoids or the combination of high-dose glucocorticoids and another immunosuppressive agent to achieve disease control [
Immunosuppressive agents are also used if inﬂammation recurs during prednisone taper at doses too high for long-term treatment, if signiﬁcant side effects are incurred during prednisone therapy, or if a systemic condition requires immunosuppressive agents.Cyclophosphamide is among the most commonly used agents, because of its established use in vasculitides. Patients are started on cyclophosphamide at a dose of 2 mg/kg/d, in conjunction with prednisone at 1 mg/kg/d. The prednisone can then be tapered over the ﬁrst 4 to 8 weeks of therapy. Complete blood counts and urinalysis are monitored regularly, initially weekly and then monthly
Remission was defined as control of scleral inflammation while receiving acyclovir therapy without concomitant administration corticosteroid therapy.