Sections

Psoriasis

Medication

Medication Summary

Many drugs that affect the rate of skin cell production are used in psoriasis therapy alone or in combination with light therapy, stress reduction, and climatotherapy. Adjuncts to treatment include sunshine, moisturizers, and salicylic acid as a scale-removing agent. Generally, these therapies are used for patients with less than 20% of body surface area involved, unless the lesions are physically, socially, or economically disabling.

Treatments for more advanced psoriasis include narrowband ultraviolet B (UVB) light, psoralen with ultraviolet A (UVA) light retinoids (eg, isotretinoin [Accutane, Claravis], acitretin [Soriatane]), methotrexate (particularly for arthritis), cyclosporine (Neoral, Sandimmune), infliximab (Remicade), etanercept (Enbrel), adalimumab (Humira), apremilast (Otezla), and secukinumab (Cosentyx). Decreased effectiveness of infliximab or adalimumab in a patient previously well controlled on the medication may mean that antibodies to the medication are being produced.^[63]

In a study of ustekinumab in patients with moderate-to-severe psoriasis, investigators did not observe an increased trend in dose-related or cumulative toxicity with the duration of ustekinumab treatment. The investigators also reported rates of adverse events generally comparable to those of other biologics approved for managing moderate-to-severe psoriasis.^[2] It is approved in two dosages, administered subcutaneously, with the higher dose given to those weighing 100 kg (220 pounds) or more. It has been suggested that 91 kg (200 pounds) might be a better cutoff for the higher dose for optimal control.^[3]

Recommendations from a 2013 international consensus report on treatment optimization and transitioning for moderate-to-severe plaque psoriasis include methotrexate and cyclosporine, biologic agents, and combination therapy.^[7]

The AAD guidelines recommend treatment with methotrexate, cyclosporine, and acitretin, with consideration of the contraindications and drug interactions noted in the discussion of each medication below.^[6]

Many other medications are used off label for psoriasis. Many of these are drugs approved initially for rheumatoid arthritis or inflammatory bowel disease but are found to also have benefits in skin psoriasis. Tofacitinib citrate, a Janus kinase inhibitor, is such a medication that has shown promise in the treatment of psoriasis.^[64]Caution must be taken any time a medication is used off label because the true risks and benefits may not yet have been defined for a different patient population than that originally studied.

Class Summary

Topical corticosteroids are the mainstay of treatment for mild and limited psoriasis. They can reduce plaque formation. These agents have anti-inflammatory effects and may cause profound and varied metabolic activities.

The strength of topical steroid and vehicle are chosen according to the thickness of plaques and body location. No topical corticosteroids are conclusively superior in efficacy or adverse effects than others in the same class. Some formulations such as foams and solutions are easier to use in the scalp than either creams or ointments. A patient who has been doing well on a topical steroid who begins to have worsening, especially with itching, should be evaluated for either a concomitant fungal infection or the development of allergic contact dermatitis to a steroid or vehicle component. Potent and superpotent corticosteroids generally only need be applied once daily unless the scale on a plaque is particularly thick. Extended use of very potent steroids should be avoided when possible in the treatment of genital and inverse psoriasis.

Triamcinolone topical (Kenalog Orabase, Kenalog topical, Pediaderm TA)

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Triamcinolone treats inflammatory dermatosis responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. It has mild potency and is the first drug of choice for most patients.

Betamethasone topical (Alphatrex, BetaVal, Dermabet)

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Betamethasone treats inflammatory dermatosis responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability. It is a potent topical steroid and is the drug of choice if psoriasis is resistant to milder forms.

Halobetasol (Bryhali, Lexette, Ultravate)

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This is available as lotion and foam preparations for the treatment of plaque psoriasis.

Class Summary

A topical aryl hydrocarbon receptor (AhR) agonist is a steroid-free option for initiating topical treatment. Tapinarof is the first AhR agonist approved by the FDA. Approval was based on the PSOARING clinical trials that compared use versus topical placebo. Approximately 35-40% of patients who received active drug had clear or almost clear scores after 12 weeks, compared with 6% of patients on placebo.^[65]

Tapinarof topical (Vtama)

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Efficacy of tapinarof in psoriasis is attributed to its binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of proinflammatory cytokines, including interleukin 17. It is indicated for topical treatment of adults with plaque psoriasis.

Class Summary

Ophthalmic corticosteroids treat conjunctival, corneal, and anterior chamber inflammation. These agents help control infiltration and delay vascularization. Care must be taken with long-term use because of concerns about infection with viruses such as herpes simplex or fungal infections.

Prednisolone acetate ophthalmic (Pred Forte, Pred Mild, Omnipred)

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Prednisolone decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

In cases of bacterial infections, concomitant use of anti-infective agents is mandatory; if signs and symptoms do not improve after 2 days, reevaluate patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely.

Dexamethasone ophthalmic (Maxidex, Ozurdex)

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Dexamethasone is used for various allergic and inflammatory diseases. It decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reducing capillary permeability.

Class Summary

Coal tar is an inexpensive treatment that is available over the counter in shampoos, lotions, creams, or foam for use in widespread areas of involvement. It is particularly useful in hair-bearing areas. Some recent research has shown the 1% concentration may be superior in control of lesions to more concentrated preparations. Tar preparations may be especially useful when combined with topical corticosteroids. This may be accomplished by applying the products sequentially or, when available, obtaining them from a compounding pharmacy. Treatment with tar preparations may be especially useful when combined with topical corticosteroids.

Coal tar 0.5-33% (DHS Tar, Balnetar, Cutar, Polytar, Theraplex T)

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Coal tar is antipruritic and antibacterial and inhibits deregulated epidermal proliferation and dermal infiltration. It does not injure the normal skin when applied widely, and it enhances the usefulness of phototherapy. It generally is used as a second-line drug therapy due to messy application, except for shampoos, which may be used and rinsed at once.

Class Summary

Keratolytic agents are used to remove scale, to smooth the skin, and to treat hyperkeratosis.

Removing the thick scale allows topical corticosteroids and other topical medications to better reach the target tissues and achieve better results. This is especially important on the scalp. Many over-the-counter preparations can be used for this, most of which contain salicylic acid. Lactic acid, ammonium lactate, and urea are other ingredients that may be applied before or at the same time as other topical medications. Urea preparations stronger than 30% require a prescription, a variety of creams, lotions, and foams are available for this. Many “foot creams” contain combinations of keratolytics and may be applied to any area of the body needing scale removal.

Anthralin is also considered to be in the antipsoriatic therapeutic class.

Anthralin (Dritho-Creme, Zithranol)

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Anthralin reduces the rate of cell proliferation. Its chemically reducing properties may also upset the oxidative metabolic processes, further reducing epidermal mitosis. It is not the first or second drug of choice due to irritation problems of normal skin surrounding lesions and staining of the skin.

Class Summary

Vitamin D analogs are used in patients with lesions resistant to topical therapy or with lesions on the face or exposed areas where thinning of the skin would pose cosmetic problems. These come as ointments, solutions, and foams. The latter two are especially useful for scalp treatments.

Calcitriol ointment (Vectical)

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Calcitriol is a topical vitamin D analog similar to calcipotriene but seems to be less irritating in sensitive areas of skin.

Calcipotriene (Dovonex, Sorilux, Calcitrene)

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Calcipotriene is a synthetic vitamin D-3 analog that regulates skin cell production and development. It is used in the treatment of moderate plaque psoriasis. This treatment does not cause long-term skin thinning or systemic effects. Sorilux is a newer foam version of this medication.

Calcipotriene/betamethasone (Enstilar, Taclonex Ointment, Taclonex Topical Suspension)

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Calcipotriene is a synthetic vitamin D-3 analog that regulates skin cell production and development. It inhibits epidermal proliferation, promotes keratinocyte differentiation, and has immunosuppressive effects on lymphoid cells. Betamethasone is a corticosteroid that decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. The combination is available as a topical ointment, foam, or as a solution that can be applied to the body or scalp. The products contain calcipotriene 0.005% and betamethasone dipropionate 0.064%.

The combination product is quite expensive and the same results may be obtained by using a generic corticosteroid sequentially in combination with one of the other vitamin D analog products.

Class Summary

Aqueous gel formulations are odorless and colorless, and no long-term skin damage has been noted with topical retinoids. There is also no threat of worsening if the therapy is withdrawn, as with steroids. These drugs should not be used in women if pregnancy is a possibility.

Tazarotene (Tazorac Fabior, Avage)

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Tazarotene is a retinoid prodrug that is converted to its active form in the body and modulates differentiation and proliferation of epithelial tissue and perhaps has anti-inflammatory and immunomodulatory activities. It may be the drug of choice for those with facial lesions who are not at risk of pregnancy.

Tazarotene, although topical, is a category X medication. Topical tretinoin is of less use in psoriatic patients. A strategy that may be tried in patients who experience unacceptable irritation is to use short contact times. There are several protocols, but the least irritating is to apply the medication for 15-20 min and then wash off. The total time on may be increased by 15-20 minutes every few weeks until clinical efficacy or adverse cutaneous effects are seen. This short-contact method may be especially useful when one is using it in skin folds but is less effective for the plaque with very thick scale.

Class Summary

Antimetabolites inhibit cell growth and proliferation.

Methotrexate (Trexall, Otrexup, Rheumatrex)

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Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of nucleotides and thymidylate. Subsequently, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues are in general more sensitive to this effect of methotrexate.

Class Summary

Immunomodulators regulate key factors responsible for inflammatory response.

Tacrolimus topical 0.1% (Protopic)

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Topical tacrolimus has been used in the past for management of refractory atopic dermatitis. However, multiple studies have shown effectiveness with psoriasis affecting intertriginous regions as well as the face. Generally, it seems to be effective in thin-skinned areas. However, it has become somewhat of a second-line agent given other studies showing topical steroids may be more effective and potential serious disease association.

Cyclosporine (Sandimmune, Neoral, Gengraf)

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Cyclosporine is an 11-amino acid cyclic peptide and natural product of fungi. It acts on T-cell replication and activity.

Cyclosporine is a specific modulator of T-cell function and an agent that depresses cell-mediated immune responses by inhibiting helper T-cell function. Preferential and reversible inhibition of T lymphocytes in the G0 or G1 phase of cell cycle is suggested. The drug binds to cyclophilin, an intracellular protein, which, in turn, prevents formation of interleukin (IL)-2 and the subsequent recruitment of activated T cells.

Cyclosporine has about 30% bioavailability, but there is marked interindividual variability. It specifically inhibits T-lymphocyte function with minimal activity against B cells. Maximum suppression of T-lymphocyte proliferation requires that the drug be present during first 24 h of antigenic exposure.

Cyclosporine suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions (eg, delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft versus host disease) for a variety of organs.

Cyclosporine is used in extensive disease refractory to other treatments, especially when used at 5 mg/kg/d. Remission is usually rapid with this therapy; however, skin lesions tend to recur within days to weeks after treatment is stopped (although patients do not usually have the severe rebound that patients withdrawing from therapy may have). Maintenance therapy (3 mg/kg/d) usually is required with lower doses of this drug.

Class Summary

These agents neutralize the effects of tumor necrosis factor-α (TNF-α). For adalimumab, weight-based dosing regimens exist for pediatric-aged patients. For etanercept, some patients will require twice-weekly dosing of the induction period indefinitely in order to maintain satisfactory control. Decreased effectiveness of infliximab or adalimumab in a patient previously well controlled on the medication may mean that antibodies to the medication are being produced.

Infliximab (Remicade)

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Infliximab is a chimeric antibody that binds both the soluble and transmembrane TNF-α molecules, thereby neutralizing the effects of TNF-α. It is indicated for chronic severe (ie, extensive and/or disabling) plaque psoriasis in adults who are candidates for systemic therapy and when other systemic therapies are medically less appropriate. It is also indicated to reduce signs and symptoms, and to improve physical function of patients with psoriatic arthritis. Screen patients for tuberculosis (TB) and hepatitis B, as reactivation of both illnesses is associated with TNF-α inhibitors.

This drug is delivered by infusion only.

Etanercept (Enbrel, Erelzi, etanercept-szzs)

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Etanercept is a recombinant human TNF-α receptor protein fused with the Fc portion of IgG1 that binds to soluble and membrane-bound TNF-α, thereby neutralizing the effects of TNF-α. It is indicated for adults and children aged 4 years and older with moderate-to-severe psoriasis. It is also indicated for adults with moderate-to-severe psoriatic arthritis. Screen patients for TB and hepatitis B, as reactivation of both illnesses is associated with TNF-α inhibitors.

Adalimumab (Humira)

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Adalimumab is a fully human anti–TNF-α monoclonal antibody. It binds specifically to soluble and membrane-bound TNF-α, thereby neutralizing the effects of TNF-α. It is used to treat moderate-to-severe psoriasis and moderate-to-severe psoriatic arthritis. Screen patients for TB and hepatitis B, as reactivation of both illnesses is associated with TNF-α inhibitors.

Class Summary

The mechanisms by which phosphodiesterase-4 (PED4) inhibitors elicit anti-inflammatory effects are not completely understood. Unlike biologics that neutralize inflammatory mediators at the protein level, apremilast modulates mediator production at the level of mRNA expression.

Apremilast (Otezla)

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Apremilast is a phosphodiesterase-4 inhibitor specific for cAMP, resulting in increased intracellular cAMP levels. It may affect cytokines and chemokine synthesis, leading to anti-inflammatory effects. It is indicated for moderate-to-severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.

Class Summary

Inhibition of PDE4 (a major cyclic 3′,5′-adenosine monophosphate (cyclic AMP) metabolizing enzyme) activity leads to accumulation of intracellular cyclic AMP. Specific mechanism(s) by which roflumilast exerts its therapeutic action for plaque psoriasis is not well defined.

Roflumilast topical (Zoryve)

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Indicated for plaque psoriasis, including intertriginous areas, in adults and adolescents.

Class Summary

Interleukins play key roles in the pathogenesis of plaque psoriasis.

Secukinumab (Cosentyx)

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Secukinumab is a human IgG1 monoclonal antibody that selectively binds to and neutralizes the proinflammatory cytokine IL-17A. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses and plays a key role in the pathogenesis of plaque psoriasis. Following the initial once-weekly SC dosage regimen, the drug is given as a maintenance dose once monthly. It is indicated for moderate-to-severe plaque psoriasis in patients who are candidates for systemic therapy or phototherapy.

Ixekizumab (Taltz)

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Ixekizumab is a humanized monoclonal IgG4 antibody that targets IL-17A and neutralizes the proinflammatory effects of IL-17A. It is administered as a SC injection. It is indicated for adults with moderate-to-severe plaque psoriasis.

Brodalumab (Siliq)

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Brodalumab is a human monoclonal IgG2 antibody that selectively binds to the human IL-17A receptor and inhibits its interactions with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25. It is indicated for moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies.

Ustekinumab (Stelara)

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Ustekinumab is a human monoclonal antibody directed against IL-12 and IL-23, thereby interfering with T-cell differentiation and activation and subsequent cytokine cascades. It is indicated for moderate-to-severe plaque psoriasis.

Risankizumab (Skyrizi, risankizumab-rzaa)

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Risankizumab is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds to the p19 subunit of human interleukin 23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses. It is indicated for treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Guselkumab (Tremfya)

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Guselkumab is a human monoclonal IgG1-lambda antibody that selectively binds to the p19 subunit of IL-23. IL-23 is a natural cytokine associated with inflammatory and immune responses. Guselkumab inhibits the proinflammatory actions of IL-23, thereby decreasing cytokine and chemokine release. It is indicated for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Tildrakizumab (Ilumya, Tildrakizumab-asmn)

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This humanized IgG1/k monoclonal antibody selectively binds to the p19 subunit of IL-23 and inhibits its interaction with the IL-23 receptor. IL-23 is a natural cytokine associated with inflammatory and immune responses. Tildrakizumab inhibits the release of proinflammatory cytokines and chemokines. It is indicated for adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Spesolimab (Spevigo)

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Anti-interleukin-36 (IL-36) monoclonal antibody; binding to the IL-36 receptor decreases release of proinflammatory and profibrotic pathways in patients with inflammatory dermatoses. Indicated for treatment of adults with generalized pustular psoriasis (GPP) flares.

Class Summary

Combination topical products with differing mechanisms of actions are available to improve ease of application.

Halobetasol/tazarotene (Duobrii)

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This combination is indicated for the treatment of plaque psoriasis in adults. It is a combination lotion containing a topical corticosteroid and a retinoid.

Class Summary

Intramuscular corticosteroids are not recommended for the management of psoriasis because of the risk of flare upon withdrawal. On the other hand, isolated plaques may be injected intralesionally, as may the nail matrix in cases of severe psoriatic nails.

Triamcinolone (Kenalog, Aristospan)

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For inflammatory dermatosis responsive to steroids; decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing capillary permeability. Many other topical steroids also are available.

Up to 0.4 mL may be injected, after ring block, into the nail bed and matrix to improve psoriatic dystrophy. Results may be long lasting but more than one treatment may be required.

Class Summary

Artificial tears are used to treat dry eye irritation. Many types of artificial tears are available over the counter. In mild cases, preserved tears can be used. In severe cases, only nonpreserved tears should be used. Preserved tears include GenTeal, Refresh Tears, and Tears Naturale II. Nonpreserved tears include Refresh, Refresh Plus, OcuCoat, Bion, and Hypo Tears PF.

Artificial tears (Tears Naturale Forte, BionTears, HypoTears, Murine Tears)

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Artificial tears contain the equivalent of 0.9% NaCl and are used to maintain ocular tonicity. They act to stabilize and thicken precorneal tear film and prolong tear film breakup time, which occurs with dry eye states.

Questions

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Media Gallery

Plaque psoriasis is raised, roughened, and covered with white or silver scale with underlying erythema. Contributed by Randy Park, MD.
Guttate psoriasis erupted in this patient after topical steroid therapy was withdrawn during a pregnancy. Contributed by Randy Park, MD.
Plaque psoriasis is most common on the extensor surfaces of the knees and elbows. Contributed by Randy Park, MD.
Nail psoriasis. Pits, distal onycholysis (nail separation), and brownish staining ("oil spots") are classic nail findings
Inverse psoriasis. Occurring in skin folds, this will often lack the scale seen in other locations.
Pustular psoriasis of the soles. This may be confined to the hands and feet (Acrodermatitis Continua of Hallepeau) or may be part of a generalized pustular psoriasis (Von Zumbusch disease)

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Author

Jacquiline Habashy, DO, MSc Resident Physician, Department of Dermatology, Western University of Health Sciences College of Osteopathic Medicine of the Pacific

Jacquiline Habashy, DO, MSc is a member of the following medical societies: American Osteopathic College of Dermatology

Disclosure: Nothing to disclose.

Coauthor(s)

David T Robles, MD, PhD, FAAD Director, Dermatology Division, Chaparral Medical Group

David T Robles, MD, PhD, FAAD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Received income in an amount equal to or greater than $250 from: Elsevier; WebMD<br/>Served as a speaker for various universities, dermatology societies, and dermatology departments.

Additional Contributors

Jeffrey Meffert, MD † Former Associate Clinical Professor of Dermatology, University of Texas School of Medicine at San Antonio

Jeffrey Meffert, MD is a member of the following medical societies: American Academy of Dermatology, American Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Acknowledgements

Robert Arffa, MD Clinical Assistant Professor, University of Pittsburgh School of Medicine

Robert Arffa, MD is a member of the following medical societies: American Academy of Ophthalmology