· Peter A. Rapoza, MD with Claudia M. Francesconi, MD Boston
With interrogation, observation and analysis, you can resolve
the majority of these cases.
To solve complex mysteries like the Sign of the Four and the Hound of the Baskervilles, Sherlock Holmes used interrogation, observation, high-tech lab tests of his own invention, and his keen powers of analysis. His techniques can be instructive when we face cases of ocular hyperemia that have lasted for more than two weeks. On the surface, these cases are anything but elementary. But by assembling all the facts and then analyzing them carefully, you can usually solve these perplexing cases. In this article, I'll provide advice on how.
Interrogation
Probably the most important part of the diagnostic process is the history. Here are a few tips on evaluating:
· Age. This information can help you narrow your investigation.
When neonates have chronic red eye, clearly the leading possibility is a disease associated with the birth process, including chlamydia, gonoccus or herpes simplex. The latter can be fatal, so fast action is necessary.
In young children, virus is by far the most common cause of chronic red eye. However, bacterial infections are also relatively common, particularly Haemophilus. Do not forget about the possibility of sexual abuse and resulting sexually transmitted disease. Some children present with red eye secondary to chlamydia or gonorrhea.
In kids 10 to 15 years of age, a common cause of persistent, painful red eye is vernal keratoconjunctivitis.
In patients who are sexually active and/or promiscuous, always consider the possibility of sexually transmitted disease. Don't forget that sexual activity is occurring at younger ages these days.
Keratoconjunctivitis sicca occurs to many patients in middle and advanced age, but is particularly common in women going through menopause.
Blepharitis typically is a disease of older patients, as is exposure keratopathy secondary to lid malformations.
· Symptoms Listen carefully to what the patient tells you.
Itching almost always indicates a form of allergic conjunctivitis. Pain indicates a deeper process, and may mean corneal ulcer, perforation, foreign body, or corneal viral infection like EKC.
Photophobia typically indicates intraocular inflammation.
Discharge can be important. Clear discharge typically means an allergic or viral process. Purulent discharge indicates the presence of polymorphonucleocytes in the tear film, an indicator of bacterial infection or chlamydia.
A complaint of blurry vision may simply indicate inconsistent tear film, but rule out corneal processes, including ulcer, EKC and the like.
Do the symptoms occur in one or both eyes? Allergic conjunctivitis should be bilateral, unless the patient is using ocular medications in just one eye. Infectious disorders like bacterial conjunctivitis and herpes simplex are most often unilateral, although exceptions abound. Foreign bodies are most often unilateral. Highly infectious diseases like EKC and gonorrheal conjunctivitis often begin in one eye and then get transferred to the fellow eye.
· Environment. Often, you can pick up clues to a disease by questioning patients about their environments.
Is the patient constantly exposed to low humidity? Pilots and stewardesses often fall into this category. Smoke, allergens and wind can be a factor.
Certainly, airborne toxins and particulates can cause chronic red eye. Ask about anything that may involve toxic agents, including painting, boat maintenance, and swimming without goggles.
More and more, I find the source of chronic red eyes to be pets. More than once, I've found cat hair embedded on the conjunctiva, visible only with fluorescein staining. One patient kept tarantulas as pets. When she fed the spiders, she stuck her head into the terrarium, and the tarantulas reared up and shot tiny spines into her eyes.
Obviously, it's important to ask whether the patient has been in contact with others who've had red eyes. Suspect virus or chlamydia if the answer is yes.
An easy one to forget is exposure to UV light. Welders, laboratory workers and patients who use tanning booths are candidates for UV keratitis.
· Contact lens use. Ask what type of lens the patient wears and what his or her lens hygiene regimen is. Improperly disinfected soft lenses in particular are excellent vectors for micro-organisms. Patients who use the wrong disinfection solutions or use them improperly can sustain allergic or toxic reactions to the solution. Patients who overwear lenses of any type can develop inflammation.
Systemic disease. A history of allergy to airborne pollens or medications can sometimes be significant. Genitourinary discharge, dysuria, or pubic lice may indicate sexually transmitted disease. Upper respiratory tract infection may indicate viral conjunctivitis.
Skin lesions or mucosal lesions may indicate herpes zoster or molluscum contagiosum. A history of rosacea may mean seborrheic blepharitis, while a history of atopy (asthma, eczema) indicates the potential for VKC.
Ask also about diseases mediated by the immune system, including connective tissue diseases like rheumatoid arthritis and lupus and ocular cicatricial pemphigoid, Stevens-Johnson syndrome and HIV.
Ask which systemic and topical medications the patient is taking. Many medications can cause drying, including hormonal supplements, antihistamines, anticholinergics, and psychotropics.
· Makeup. If you suspect infection and the patient uses mascara, consider the possibility that it may be infected. Sometimes, women borrow the mascara of someone else and sustain an eye infection in this way.
· Timing of the symptoms. If the problem is dry-eye related, the symptoms will be at their most tolerable in the morning and then get worse as the day goes on.
Observation
Once you have done a thorough history, proceed to the exam.
Personally, I like to first always document visual acuity.
Next, I examine the patient's skin. In the periocular area, I look for black "allergic shiners," areas of broken capillaries from excessive rubbing. I also look at the eyelids, trying to see if they are malpositioned, loose, or if the patient has Bell's palsy. I briefly examine the rest of the face and hands, looking for eczema or psoriasis which may mean atopy.
I palpate the patient's preauricular lymph nodes, looking for lymphadenopathy. This sign is often present in patients with virus or chlamydia, and present much less frequently when the infection is bacterial.
Under the slit lamp, I first look at the eyelid margins, checking for trichiasis or lashes in abnormal places. For instance, lashes occasionally emerge from a punctum or a minor lacrimal gland. I also look for evidence of inflammation, ulcers, nodules, vesicles or keratinization.
I examine the lacrimal puncta and canaliculi, and push on the nasal lacrimal sac to make sure there is no discharge indicating infection.
Next, I examine the tarsal conjunctiva. I'm looking for the presence and size of papillae. Their presence might indicate an exposed suture, an imperfection on a prosthesis, or a problematic contact lens.
I look also for follicles, an indication of viral or chlamydial disease. It can be difficult to distinguish follicles from papillae. To tell the difference, look at the vasculature closely. Papillae have a vascular stalk in the center, whereas in follicles, you will typically see vessels surrounding lymphatic material in the center.
I routinely press on the eyelids with a swab and examine the Meibomian secretions. Healthy secretions are as clear as olive oil. If nothing comes out, or plugs or pus emerge, the patient has Meibomian gland disease, a very common source of chronic red eye. You can often treat this successfully with systemic doxycycline or minocycline.
I routinely evert the eyelid to examine the palpebral conjunctiva, looking for any membranes, hemorrhages, granulomas (an uncommon indication of sarcoidosis) or foreign material. I'm sometimes amazed by what I find under the lid.
Next, I scan the bulbar and palpebral conjunctiva, looking for any gross cicatrical changes that may have resulted from a chemical or thermal burn or a serious infection.
As I am looking at the bulbar conjunctiva, I assess the degree of hyperemia, using a scale of one to four. I also assess the level of chemosis. The more chemotic the conjunctiva, the more I suspect allergy or a chemical or toxic insult.
Again, I look for the presence of follicles, which might indicate a viral or chlamydial process. I also look for nodules, or granulomas. These are very uncommon, however.
I scour the bulbar conjunctiva for foreign material. I've found everything from Weck cell sponges to seed husks to insect legs to pet hair.
I carefully examine the limbus. I'm looking to see whether there is true ciliary flush indicative of an intraocular process. I also look for phlyctenules, or collections of white cells at the limbus. These may indicate marginal keratitis secondary to Staph or tuberculosis.
I often instill fluorescein and rose bengal stains to examine the ocular surface.
You may see a wide variety of epithelial defects with fluorescein. Dendritic lesions and ulcers are quite obvious. Punctate staining can be a little more confusing. I would recommend first considering the distribution. Punctate lesions all across the surface could be due to medicamentosa, eye rubbing, or chemical keratitis. If it's only present in the inferior palpebral conjunctiva, it could be exposure keratitis secondary to lagophthalmos.
If the fluorescein seems to be adhering to small, raised corneal lesions that look like chalkmarks on a blackboard, you could be dealing with Thygeson's superficial punctate keratitis. If you see subepithelial infiltrates across the cornea, you are probably dealing with viral keratoconjunctivits.
Rose bengal, a vital dye, is excellent for diagnosing dry eye and lagophthalmos. In the former case, dead conjunctival cells will stain all across the conjunctiva. In the latter case, you will see a band of staining in the inferior sclera, sometimes just touching the cornea. Rose bengal also shows dendrites very well; the dead cells along the tree-like lesions take up the stain.
Some dry-eye patients develop corneal filaments, small "tubes" of epithelium surrounding a strand of mucus. Under the microscope, these resemble an elephant trunk. If you see one of these, don't try to pull it off; you'll end up with an epithelial defect. Instead, elevate it and then cut it at its base.
Lab Tests
In some cases, routine cytology, gram stains and Giemsa stains can help you confirm the diagnosis.
Giemsa stains can be especially helpful in determining allergy. The presence of eosinophils adds a great deal of support to the diagnosis of allergic conjunctivitis, even if the cells have ruptured. Giemsa stains are also quite good at detecting Chlamydia; the tell-tale sign is inclusion bodies in the cytoplasm. There are rapid diagnostic tests for the latter disease which are much more sensitive and specific, including Microtrak and Pathfinder.
Gram stains can be a good screening test for bacteria, but they have a fairly low yield. If you suspect a bacterial infection, consider culturing a swab or tissue scraping in reduced blood agar, thioglycate broth and possibly chocolate agar. If you suspect a fungal infection, culture in Sabaraud's agar and reduced blood at room temperature.
In patients with cicatrical pemphigoid, and when you suspect a possible conjunctival neoplasia, a conjunctival biopsy may be necessary.
Analysis
Once you have all the facts, try to match them with the most likely diagnosis.
Just a few additional tips on this topic:
· By far the vast majority of chronic red-eye cases referred to my practice are the product of either dry eye or chronic blepharitis. Especially in the middle-aged and elderly, think about these diseases first.
· Remember that some of the most mysterious chronic red eyes are self-induced. In some cases, the patient's motive is to lay out of work and collect workmen's compensation. In others, the patients are simply mentally imbalanced. One patient of mine was in the habit of inserting an aspirin under his lower eyelid for hours at a time to produce the requisite inflammation.
· Pay special attention to the patient's occupations and avocations. As I become older and wiser, I find that factors involved with one or both are responsible for chronic red eyes.
· Recognize that in some cases, you may never diagnose the cause. While at the Wilmer Eye Institute, I studied 58 chronic red-eye cases. In 31 percent, a cause was never identified.
· Do not attempt to "diagnose by treating." Establish a diagnosis first. "Shotgun" treatment interferes with cultures and results in medicamentosa more often than it solves the problem.
· Perspiration is a lot more important than inspiration when working up one of these cases. Clinicians who take the time necessary to listen, examine and think will nearly always find the source of chronic ocular hyperemia.
Dr. Rapoza, who serves as an assistant clinical professor at
the Harvard Medical School, is in private practice.
The Case of the
Multiple Malady
A 54-year-old woman complained of a six-month history of conjunctivitis in the left eye only. Another physician had tried an antibiotic-steroid combination and a two-week course of doxycycline 100 mg bid po. Unfortunately, each time the physician tapered the steroid, the inflammation reappeared.
A visual acuity test produced corrected acuities of 20/20 in both eyes. My slit-lamp exam revealed trace injection in the right eye as well as grade 1 to 2 injection in the left. Approximately 90 percent of the Meibomian glands were occluded. When I expressed them, the secretions were turbid.
There were 1+ follicles in the right eye and 2+ follicles in the left. I palpated the preauricular lymph nodes, and found lymphadenopathy on the left side.
My first impression was that the patient had a chronic adenoviral conjunctivitis of the left eye, and Meibomian gland disease in both eyes. However, because of the presence of the follicles, and because the inflammation had persisted for so long, I performed a Microtrak immunofluorescence assay of the left eye to test for chlamydia. The test results were negative.
I started the patient on doxycycline 50 mg bid po for one week, then tapered to qd. I also prescribed a course of fluorometholone tid, tapered to zero over three weeks.
One month later, the patient returned. She said the left eye had improved somewhat, but that both eyes were still red and irritated.
I felt the viral infection had resolved. But my slit lamp exam showed that the Meibomian glands had not improved. Moreover, when I instilled rose bengal stain, I observed 1 to 2+ uptake all across the ocular surfaces in both eyes. I decided to perform a Schirmer test under topical anesthetic. The patient produced only 2 mm of wetting in both eyes.
To see if punctal occlusion would aid with the aqueous deficiency, I placed diagnostic collagen canalicular plugs in all four canaliculi. I also switched the patient from doxycycline to minocycline, 100 mg/day. Minocycline is significantly more expensive, but more lipophilic and better able to penetrate sebaceous glands.
Two weeks later, the patient returned, saying her symptoms had improved by about 50 percent. The Meibomian gland secretions had thinned, and now 50 percent of the glands were open. There was no epiphora. I placed Herrick plugs in the inferior canaliculi in both eyes, and asked the patient to continue with the minocycline. Two months later, the patient reported 100 percent improvement of her symptoms. Her eyes were white and quiet. Half of her Meibomian glands remained obstructed, but the secretions were clearer.
Potential causes of Chronic Ocular Hyperemia
Category Specific Diagnoses
Ocular Surface Disease
Allergy
Viral
Bacterial
Chlamydial
Mechanical
Environmental
Neoplasm
Corneal inflammation
Man-made
Other
· Aqueous deficiency (Keratoconjunctivitis Sicca), often secondary to hormonal change, connective tissue disorders like rheumatoid arthritis and lupus, and systemic medications such as hormonal supplements, antihistamines, anticholinergics, and psychotropics.
· Lipid deficiency, secondary to blepharitis (anterior marginal, posterior marginal and Staph and Seborrheic varieties) or lid abnormalities (entropion, ectropion, prior blepharoplasty).
· Exposure keratitis, secondary to proptosis (Thyroid disease) or floppy lid syndrome
· Mucin deficiency (secondary to chemical or radiation burn or severe viral conjunctivitis)
· Vernal keratoconjunctivitis
· Seasonal allergic conjunctivitis
· Contact-lens associated GPC
· Adenovirus
· Varicella zoster (measles)
· Mumps
· Herpes zoster (chickenpox, shingles)
· Herpes simplex keratitis
· Strep
· Staph
· Gonorrhea
· Haemophilus
· Lyme disease
· Chlamydia trachomatis
· Chlamydia tisittaci
· Eyelash
· Foreign body
· Toxins/Particulates in workplace or home, including fiberglass particles and pet hair.
· Carcinoma in situ
· Bacterial infection
· Viral infection
· Acanthamoeba
· Melt secondary to autoimmune disease
· Medicamentosa
· Self-induced/Malingering
· Angle-closure glaucoma
· Episcleritis
· Sinus fistula
· Intraocular inflammation
The Case of the
Hidden Lesion
A 38-year-old investment banker came to me for a dry eye work-up, on referral from an optometrist. The patient said he had been experiencing irritation in both eyes, but said the symptoms were most pronounced in the right eye.
After establishing that he could see 20/20 with correction, I performed my normal gross examination of the adnexa. I saw nothing.
A slit-lamp exam revealed trace conjunctival injection in both eyes, but no significant follicles or papillae. When I instilled rose bengal stain, I saw only trace uptake across both ocular surfaces. A Schirmer test produced only 5 mm of wetting in each eye.
I felt the patient had borderline dry eye, and suggested artificial tears. However, the patient said he had extreme difficulty with instilling drops in his eyes. For this reason, I decided to place diagnostic collagen plugs in all four punctae.
One week later, the patient returned, saying that he had experienced only slight improvement. There was no epiphora, however, so I placed silicone plugs in the lower canaliculae.
Two weeks later, the patient returned, complaining that his eyes still felt irritated. By this time, I could clearly see follicles in the inferior right palpebral conjunctiva. There were no other findings, so I suggested that the patient try a course of artificial tears three to four times a day, and return in two weeks.
When he returned, there was marked conjunctival injection in both eyes, an increased bilateral follicular response, and one molluscum contagiosum lesion on both the right upper lid and the lower left lid margins. I excised them both under local anesthetic. One week later, the symptoms resolved. Interestingly, the patient was monogamous and did not remember contact with anyone who suffered from red eye.
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