Ocular rosacea therapy ranges from tetracycline to steroids

Ocular symptoms are a frequent aspect of rosacea and often appear as over-expressed inflammatory markers in the conjunctiva.

“Our practice has an exceedingly high prevalence of patients with ocular manifestations of rosacea,” said Joseph P. Shovlin, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at the Northeastern Eye Institute in Scranton, Pa. “Inflammatory markers such as cytokines, matrix metalloproteases, T-helper/inducer cells and antigen-presenting cells have been found in the conjunctivae of rosacea patients.”

Practitioners are using several different treatment approaches to this chronic inflammatory disease, including Restasis (0.05% cyclosporine A, Allergan), steroid drops, oral tetracyclines and topical agents such as metronidazole.

Differential diagnosis

The location of the redness, pustules and telangiectasia on the face is key to making the diagnosis of rosacea, according to Paul M. Karpecki, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at Moyes Eye Center in Kansas City.

“Women tend to show signs on the cheeks and chin, and men show signs on the nose and sometimes forehead,” he said in an interview with Primary Care Optometry News. “It is important to make the right diagnosis in women, because lupus presents as a rash or redness on the cheeks as well, but, unlike rosacea dermatitis, it does not show the pustules or teleangiectasia.”

Dr. Karpecki said the rash in lupus is known as a butterfly rash due to its appearance as it covers the cheeks.

“In rosacea, the hallmarks are essentially pimples or acne and prominent red blood vessels or telangiectasia,” he said.

Dr. Karpecki said other differentials include acne vulgaris, which is the typical acne often encountered in puberty. The difference is that acne vulgaris has comedones (whiteheads), which do not occur in rosacea, he said.

“Also, acne rosacea has triggers, such as spicy foods, hot drinks or alcohol,” he said, “and acne rosacea tends to affect an older population (age 30 to 60), with the median age being in the late 40s or 50s.”

The use of Restasis

Restasis, used off-label, has demonstrated positive results in the treatment of ocular rosacea, according to Dr. Shovlin.

“Several investigators have reported an improvement in ocular surface by reducing inflammation with topical cyclosporine,” he told Primary Care Optometry News in an interview. “Topical cyclosporine has been shown to significantly suppress the number of activated T-lymphocytes within the conjunctiva. Its dual action of increasing tear production and reducing activated lymphocytes results in an overall reduced inflammation of the ocular surface.”

Dr. Shovlin cited a report by Perry and Donnenfeld that found that topical cyclosporine was effective in treating ocular rosacea unresponsive to conventional therapy.

“This has been our experience with a significant number of patients,” he said. “A large number have even been able to discontinue all other medications (topical and oral) after 4 to 6 months of cyclosporine and seem to be well-maintained with twice-daily dosing.”

J. James Thimons, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at Ophthalmic Consultants of Connecticut in Fairfield, also cited a study by Wittpenn and colleagues examining the treatment of chronic ocular rosacea with Restasis. The study found that 39% of rosacea patients enrolled required no medications in addition to Restasis, with 61% continuing with low-dose tetracyclines in addition to the Restasis.

The authors recommended that further research evaluate Restasis as a first-line therapy for ocular rosacea.

“This study came to the conclusion that Restasis is a very effective drug and is able to manage a substantial number of patients without steroids,” Dr. Thimons told PCON. (Perry HD, Whittpenn JR, ARVO 2005)

Tear components may indicate ocular rosacea

Scientists may have discovered new clues to help identify the ocular effects of rosacea.

Mark Mannis, MD, chairman of ophthalmology at the University of California, Davis, and colleagues collected samples of tears from 16 ocular rosacea patients and 21 individuals without rosacea. The researchers analyzed the tears for the presence of oligosaccharides, according to a press release from the National Rosacea Society. Oligosaccharides, especially those found in mucus, are known to be sensitive to the biochemical environment and, therefore, could be an indicator of disease states, according to the press release.

The researchers discovered that the presence of high levels of oligosaccharides in human tears may be a diagnostic indication of ocular rosacea, and that high levels of 13 particular types of the compound were associated with rosacea and may serve as more specific markers for the disorder. Because a general increase of oligosaccharides may not necessarily be specific to rosacea, the researchers emphasized that the types of oligosaccharides found in greatest abundance in rosacea patients should be evaluated in further research for their specificity as markers for ocular rosacea.

“We plan to further investigate which types of oligosaccharides are the best indicators of rosacea in order to achieve even greater accuracy in distinguishing ocular rosacea from normal patients,” Dr. Mannis said.

Oral tetracyclines

Dr. Karpecki said he has found a great deal of success in treating rosacea patients with oral tetracyclines. “This is a necessary treatment for the dermatologic component and is very beneficial in treating the ophthalmic component as well,” he said.

Dr. Karpecki said his preference is a lower dose, such as 50 mg or 20 mg (Periostat, CollaGenex Pharmaceuticals), of doxycycline, which appears to decrease side effects such as gastritis or esophagitis.

“Other ways to minimize the gastritis/esophagitis is to have the patient take the second pill a few hours before going to bed, rather than right before sleep,” he said, “as the undissolved medication could lead to a localized inflammatory response when the patient is in a supine position.”

Doxycycline monohydrate seems to be better tolerated than doxycycline hyclate for most patients, Dr. Shovlin added.

Dr. Karpecki discussed risks and contraindications associated with oral tetracyclines. He said sunburn or phototoxicity can be aggravated by these drugs. “Even with the lower doses, this needs to be addressed with each patient, and they should wear long-sleeved clothing or use sunscreen,” he said.

He also advised against the use of oral tetracyclines for women who are pregnant or nursing, as well as for children.

Dr. Karpecki attributed the success of oral tetracyclines in rosacea patients to its accumulation in the oil glands and its cytokine-inhibiting abilities.

“I believe the response has been very good to systemic tetracycline because of its strong anti-inflammatory abilities,” he said. “It is actually a relatively ineffective antibiotic, but its ability to accumulate in oil glands, suppress cytokines or inflammatory mediators and regulate enzymatic activity makes it very potent in oil gland disease.”

The use of steroids

Steroids are another approach to treating rosacea, either in combination with an antibiotic or alone. “I suppose you can divide doctors into those who are steroid-shy — as we are trained to be — and those who are not,” said Charles B. Slonim, MD, FACS, an affiliate professor of ophthalmology at the University of South Florida College of Medicine, Tampa. “Those of us who are purists feel comfortable using a steroid without a topical antibiotic, but many will add an antibiotic because they want to be careful.”

Dr. Slonim said pure rosacea blepharitis is an inflammatory process, not an infectious one.

“If I feel there is an infectious component, I will add an anti-infective such as tobramycin, which works very nicely in combination with loteprednol under the name Zylet (Bausch & Lomb),” he said. “But I will switch to just the loteprednol (Lotemax, Bausch & Lomb) after I feel comfortable that the suspected infectious process is gone. Generally, I don’t consider rosacea to be an infectious process.”

Dr. Slonim said he feels comfortable using a steroid alone, and his steroid of choice is loteprednol. “I like its efficacy and its good safety profile,” he said. “Many of these patients need to be on a medication for a long time, and with loteprednol, I don’t have a fear of major side effects such as intraocular pressure increase or cataract formation.”

He said loteprednol also has no “rebound effect,” as is often the case with many of the currently available ketone (non-ester) steroids. “In clinical studies, even after it was stopped suddenly after 4 to 6 weeks of usage, there were no reported rebound phenomena with this product,” he said.

Dermatologic approaches

Topical therapy may also be useful in treating ocular surface rosacea. Metronidazole, one of the most widely used topical drugs, is available as a cream, gel or lotion. Products include MetroGel 1% (Galderma Labs, Fort Worth, Texas), MetroCream 0.75% (Galderma), MetroLotion 0.75% (Galderma) and Noritate 1% cream (Aventis Pharma, Laval, Quebec).

Dr. Thimons, a rosacea sufferer himself, said he prefers MetroCream to the gel version of the drug. “I like the cream because it does not have a visible cosmetic endpoint,” he said. “The gel left my skin looking shiny like I had just put on an ointment. I prefer the cream on a cosmetic level because it isn’t as noticeable.”

He said both cream and gel are equally effective in fighting ocular surface inflammation. “Most of the symptoms of rosacea are related to inflammation and its subsequent effect on the ocular surface,” he said. “Metronidazole is a drug that is active against the Staphylococcus organism. It basically depletes the surface inflammation that initiates the symptomatic changes.”

For more information:
  • Joseph P. Shovlin, OD, FAAO, is a Primary Care Optometry News Editorial Board member. He can be reached at Northeastern Eye Institute, 200 Mifflin Ave., Scranton, PA 18503; (570) 342-3145; fax: (570) 344-1309; e-mail: jshovlin@aol.com.
  • Paul M. Karpecki, OD, FAAO, is a Primary Care Optometry News Editorial Board member. He can be reached at Moyes Eye Center, Barry Medical Park, St. Luke’s Northland Campus, 5844 N.W. Barry Road, Ste. 200, Kansas City, MO 64154; (816) 746-9800; fax: (913) 681-5584; e-mail: PaulK-VC@kc.rr.com.
  • J. James Thimons, OD, FAAO, is a Primary Care Optometry News Editorial Board member and chairman of the National Glaucoma Society. He can be reached at Ophthalmic Consultants of Connecticut, 75 Kings Highway, Fairfield, CT 06430; (203) 334-2020; fax: (203) 330-4958; e-mail: jthimons@sbcglobal.net.
  • Charles B. Slonim, MD, FACS, is an affiliate professor of ophthalmology, University of South Florida College of Medicine, Tampa, Fla. He can be reached at 4444 E. Fletcher Ave. Ste. D, Tampa, FL 33613; (813) 971-9709; fax: (813) 977-2611; e-mail: drslonim@tampabay.rr.com. Dr. Slonim is a paid consultant for Bausch & Lomb. Drs. Shovlin, Karpecki and Thimons have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.

Ocular symptoms are a frequent aspect of rosacea and often appear as over-expressed inflammatory markers in the conjunctiva.

“Our practice has an exceedingly high prevalence of patients with ocular manifestations of rosacea,” said Joseph P. Shovlin, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at the Northeastern Eye Institute in Scranton, Pa. “Inflammatory markers such as cytokines, matrix metalloproteases, T-helper/inducer cells and antigen-presenting cells have been found in the conjunctivae of rosacea patients.”

Practitioners are using several different treatment approaches to this chronic inflammatory disease, including Restasis (0.05% cyclosporine A, Allergan), steroid drops, oral tetracyclines and topical agents such as metronidazole.

Differential diagnosis

The location of the redness, pustules and telangiectasia on the face is key to making the diagnosis of rosacea, according to Paul M. Karpecki, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at Moyes Eye Center in Kansas City.

“Women tend to show signs on the cheeks and chin, and men show signs on the nose and sometimes forehead,” he said in an interview with Primary Care Optometry News. “It is important to make the right diagnosis in women, because lupus presents as a rash or redness on the cheeks as well, but, unlike rosacea dermatitis, it does not show the pustules or teleangiectasia.”

Dr. Karpecki said the rash in lupus is known as a butterfly rash due to its appearance as it covers the cheeks.

“In rosacea, the hallmarks are essentially pimples or acne and prominent red blood vessels or telangiectasia,” he said.

Dr. Karpecki said other differentials include acne vulgaris, which is the typical acne often encountered in puberty. The difference is that acne vulgaris has comedones (whiteheads), which do not occur in rosacea, he said.

“Also, acne rosacea has triggers, such as spicy foods, hot drinks or alcohol,” he said, “and acne rosacea tends to affect an older population (age 30 to 60), with the median age being in the late 40s or 50s.”

The use of Restasis

Restasis, used off-label, has demonstrated positive results in the treatment of ocular rosacea, according to Dr. Shovlin.

“Several investigators have reported an improvement in ocular surface by reducing inflammation with topical cyclosporine,” he told Primary Care Optometry News in an interview. “Topical cyclosporine has been shown to significantly suppress the number of activated T-lymphocytes within the conjunctiva. Its dual action of increasing tear production and reducing activated lymphocytes results in an overall reduced inflammation of the ocular surface.”

Dr. Shovlin cited a report by Perry and Donnenfeld that found that topical cyclosporine was effective in treating ocular rosacea unresponsive to conventional therapy.

“This has been our experience with a significant number of patients,” he said. “A large number have even been able to discontinue all other medications (topical and oral) after 4 to 6 months of cyclosporine and seem to be well-maintained with twice-daily dosing.”

J. James Thimons, OD, FAAO, a Primary Care Optometry News Editorial Board member who practices at Ophthalmic Consultants of Connecticut in Fairfield, also cited a study by Wittpenn and colleagues examining the treatment of chronic ocular rosacea with Restasis. The study found that 39% of rosacea patients enrolled required no medications in addition to Restasis, with 61% continuing with low-dose tetracyclines in addition to the Restasis.

The authors recommended that further research evaluate Restasis as a first-line therapy for ocular rosacea.

“This study came to the conclusion that Restasis is a very effective drug and is able to manage a substantial number of patients without steroids,” Dr. Thimons told PCON. (Perry HD, Whittpenn JR, ARVO 2005)

Tear components may indicate ocular rosacea

Scientists may have discovered new clues to help identify the ocular effects of rosacea.

Mark Mannis, MD, chairman of ophthalmology at the University of California, Davis, and colleagues collected samples of tears from 16 ocular rosacea patients and 21 individuals without rosacea. The researchers analyzed the tears for the presence of oligosaccharides, according to a press release from the National Rosacea Society. Oligosaccharides, especially those found in mucus, are known to be sensitive to the biochemical environment and, therefore, could be an indicator of disease states, according to the press release.

The researchers discovered that the presence of high levels of oligosaccharides in human tears may be a diagnostic indication of ocular rosacea, and that high levels of 13 particular types of the compound were associated with rosacea and may serve as more specific markers for the disorder. Because a general increase of oligosaccharides may not necessarily be specific to rosacea, the researchers emphasized that the types of oligosaccharides found in greatest abundance in rosacea patients should be evaluated in further research for their specificity as markers for ocular rosacea.

“We plan to further investigate which types of oligosaccharides are the best indicators of rosacea in order to achieve even greater accuracy in distinguishing ocular rosacea from normal patients,” Dr. Mannis said.

Oral tetracyclines

Dr. Karpecki said he has found a great deal of success in treating rosacea patients with oral tetracyclines. “This is a necessary treatment for the dermatologic component and is very beneficial in treating the ophthalmic component as well,” he said.

Dr. Karpecki said his preference is a lower dose, such as 50 mg or 20 mg (Periostat, CollaGenex Pharmaceuticals), of doxycycline, which appears to decrease side effects such as gastritis or esophagitis.

“Other ways to minimize the gastritis/esophagitis is to have the patient take the second pill a few hours before going to bed, rather than right before sleep,” he said, “as the undissolved medication could lead to a localized inflammatory response when the patient is in a supine position.”

Doxycycline monohydrate seems to be better tolerated than doxycycline hyclate for most patients, Dr. Shovlin added.

Dr. Karpecki discussed risks and contraindications associated with oral tetracyclines. He said sunburn or phototoxicity can be aggravated by these drugs. “Even with the lower doses, this needs to be addressed with each patient, and they should wear long-sleeved clothing or use sunscreen,” he said.

He also advised against the use of oral tetracyclines for women who are pregnant or nursing, as well as for children.

Dr. Karpecki attributed the success of oral tetracyclines in rosacea patients to its accumulation in the oil glands and its cytokine-inhibiting abilities.

“I believe the response has been very good to systemic tetracycline because of its strong anti-inflammatory abilities,” he said. “It is actually a relatively ineffective antibiotic, but its ability to accumulate in oil glands, suppress cytokines or inflammatory mediators and regulate enzymatic activity makes it very potent in oil gland disease.”

The use of steroids

Steroids are another approach to treating rosacea, either in combination with an antibiotic or alone. “I suppose you can divide doctors into those who are steroid-shy — as we are trained to be — and those who are not,” said Charles B. Slonim, MD, FACS, an affiliate professor of ophthalmology at the University of South Florida College of Medicine, Tampa. “Those of us who are purists feel comfortable using a steroid without a topical antibiotic, but many will add an antibiotic because they want to be careful.”

Dr. Slonim said pure rosacea blepharitis is an inflammatory process, not an infectious one.

“If I feel there is an infectious component, I will add an anti-infective such as tobramycin, which works very nicely in combination with loteprednol under the name Zylet (Bausch & Lomb),” he said. “But I will switch to just the loteprednol (Lotemax, Bausch & Lomb) after I feel comfortable that the suspected infectious process is gone. Generally, I don’t consider rosacea to be an infectious process.”

Dr. Slonim said he feels comfortable using a steroid alone, and his steroid of choice is loteprednol. “I like its efficacy and its good safety profile,” he said. “Many of these patients need to be on a medication for a long time, and with loteprednol, I don’t have a fear of major side effects such as intraocular pressure increase or cataract formation.”

He said loteprednol also has no “rebound effect,” as is often the case with many of the currently available ketone (non-ester) steroids. “In clinical studies, even after it was stopped suddenly after 4 to 6 weeks of usage, there were no reported rebound phenomena with this product,” he said.

Dermatologic approaches

Topical therapy may also be useful in treating ocular surface rosacea. Metronidazole, one of the most widely used topical drugs, is available as a cream, gel or lotion. Products include MetroGel 1% (Galderma Labs, Fort Worth, Texas), MetroCream 0.75% (Galderma), MetroLotion 0.75% (Galderma) and Noritate 1% cream (Aventis Pharma, Laval, Quebec).

Dr. Thimons, a rosacea sufferer himself, said he prefers MetroCream to the gel version of the drug. “I like the cream because it does not have a visible cosmetic endpoint,” he said. “The gel left my skin looking shiny like I had just put on an ointment. I prefer the cream on a cosmetic level because it isn’t as noticeable.”

He said both cream and gel are equally effective in fighting ocular surface inflammation. “Most of the symptoms of rosacea are related to inflammation and its subsequent effect on the ocular surface,” he said. “Metronidazole is a drug that is active against the Staphylococcus organism. It basically depletes the surface inflammation that initiates the symptomatic changes.”

For more information:
  • Joseph P. Shovlin, OD, FAAO, is a Primary Care Optometry News Editorial Board member. He can be reached at Northeastern Eye Institute, 200 Mifflin Ave., Scranton, PA 18503; (570) 342-3145; fax: (570) 344-1309; e-mail: jshovlin@aol.com.
  • Paul M. Karpecki, OD, FAAO, is a Primary Care Optometry News Editorial Board member. He can be reached at Moyes Eye Center, Barry Medical Park, St. Luke’s Northland Campus, 5844 N.W. Barry Road, Ste. 200, Kansas City, MO 64154; (816) 746-9800; fax: (913) 681-5584; e-mail: PaulK-VC@kc.rr.com.
  • J. James Thimons, OD, FAAO, is a Primary Care Optometry News Editorial Board member and chairman of the National Glaucoma Society. He can be reached at Ophthalmic Consultants of Connecticut, 75 Kings Highway, Fairfield, CT 06430; (203) 334-2020; fax: (203) 330-4958; e-mail: jthimons@sbcglobal.net.
  • Charles B. Slonim, MD, FACS, is an affiliate professor of ophthalmology, University of South Florida College of Medicine, Tampa, Fla. He can be reached at 4444 E. Fletcher Ave. Ste. D, Tampa, FL 33613; (813) 971-9709; fax: (813) 977-2611; e-mail: drslonim@tampabay.rr.com. Dr. Slonim is a paid consultant for Bausch & Lomb. Drs. Shovlin, Karpecki and Thimons have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.