How do you tell the difference between a corneal ulcer and a Herpes simplex. The Herpes does not necessarily have to to end bulbs.

Ken Bova

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Jul 1, 2009
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How do yu tell the difference between a corneal ulcer and a Herpes simplex. The Herpes simplex does not necessarly have to have end bulbs
 
One is full of PMN's. One mostly just stains. What are you getting at? -Charlie
 
cool coincidence but just had one yesterday that didn't appear herpetic at all, just a large pool of NaFl in a generally oblong shape that I initiated q1h Besivance and then today filled in with enough epithelium to make the branches and bulbs somewhat apparent throughout

should've taken pictures and you'd have thought Dr Bova sent the patient to me ;) , how far is Uniontown from me? :)

slowed the Besivance frequence and added antiviral orals and will see how it goes

funny thing is yesterday she said she started to treat her "abrasion" with some of the bottle of drops with the brown cap she'd been given every time before but then noticed it was expired so made the appointment to see me to get a new bottle,,,, so likely this wasn't her first herpetic "abrasion"
 
Non herpetic corneal ulcers are much more painful and generally have a more acute onset. With a bacterial ulcer, they’ll say, “It started yesterday”. With herpes it’s often, “My eyes been bugging me for the past week or so…..”

Also, of course, bacterial ulcers have infiltrates.
 
Dr. Bova,

First, please let me apologize for the harsh and profane comments that I directed towards you many months ago regarding one of your posts. It was inappropriate and I will not insult you again. Also, thanks for not blocking me after my outburst.

Regarding your question, there is an excellent article in the September 2011 issue of Review of Optometry that answers practically any question you could have on this topic. It is entitled Bacterial vs. Viral: Name That Infection! and was written by Aaron Bronner, OD.

I just finished reading the piece and it is an excellent reference to learn or re-learn about the differential diagnosis of these two very different conditions.

As my friend Tom has correctly pointed out, these lesions can be similar in appearance until the clinical presentation gets worse. In other words, the pre-dendritic stage of herpes simplex is often overlooked or vague enough to create clinical confusion.

To quote from the article:

"Unfortunately, what we see more often are non-specific findings, such as injection, minimal mucous discharge, papillae or follicles (or both) and some degree of corneal infiltration, running the gamut from diffuse stromal white blood cells to a dense focal area of infiltration either with or without an overlying epithelial defect. When faced with non-specific findings, it is up to us to come to a reasonable diagnosis and form an appropriate treatment plan."

After I read the article, I was reminded of the specific regions of the cornea that play a role in the immune response to infection. In my own Review of Optometry article entitled Understanding Specular Microscopy from several years ago, I touched on the differences in endothelial anatomy between the central corneal region and the peripheral corneal region. Well, the cornea also has two distinct immunologic regions - the limbal/peripheral zone and the central zone.

The location-dependent duality of corneal immunity is the source of some fairly common differences between lesions of the periphery and lesions of the paracentral zone. For example, when the ulcer is caused by the herpes virus, if the insult is at or near the corneal periphery, the proximity to the limbus allows the immune system to more effectively contain viral activity and the characteristic dendritic appearance never develops or it may be obscured by any type of corneal infiltration.

I believe that is an important piece of information to assist in your medical decision-making.

I could go on and on, but I would simply encourage any optometrist that wants to be well-read on the question that Dr. Bova posed to just read the article and go from there...

This is a picture from one of my patients with herpes simplex. The presentation can change depending on the stage of the disease and the patient's response to treatment.

Herpes.JPG
 
Dr. Bova,

First, please let me apologize for the harsh and profane comments that I directed towards you many months ago regarding one of your posts. It was inappropriate and I will not insult you again. Also, thanks for not blocking me after my outburst.

Regarding your question, there is an excellent article in the September 2011 issue of Review of Optometry that answers practically any question you could have on this topic. It is entitled Bacterial vs. Viral: Name That Infection! and was written by Aaron Bronner, OD.

I just finished reading the piece and it is an excellent reference to learn or re-learn about the differential diagnosis of these two very different conditions.

As my friend Tom has correctly pointed out, these lesions can be similar in appearance until the clinical presentation gets worse. In other words, the pre-dendritic stage of herpes simplex is often overlooked or vague enough to create clinical confusion.

To quote from the article:

"Unfortunately, what we see more often are non-specific findings, such as injection, minimal mucous discharge, papillae or follicles (or both) and some degree of corneal infiltration, running the gamut from diffuse stromal white blood cells to a dense focal area of infiltration either with or without an overlying epithelial defect. When faced with non-specific findings, it is up to us to come to a reasonable diagnosis and form an appropriate treatment plan."

After I read the article, I was reminded of the specific regions of the cornea that play a role in the immune response to infection. In my own Review of Optometry article entitled Understanding Specular Microscopy from several years ago, I touched on the differences in endothelial anatomy between the central corneal region and the peripheral corneal region. Well, the cornea also has two distinct immunologic regions - the limbal/peripheral zone and the central zone.

The location-dependent duality of corneal immunity is the source of some fairly common differences between lesions of the periphery and lesions of the paracentral zone. For example, when the ulcer is caused by the herpes virus, if the insult is at or near the corneal periphery, the proximity to the limbus allows the immune system to more effectively contain viral activity and the characteristic dendritic appearance never develops or it may be obscured by any type of corneal infiltration.

I believe that is an important piece of information to assist in your medical decision-making.

I could go on and on, but I would simply encourage any optometrist that wants to be well-read on the question that Dr. Bova posed to just read the article and go from there...

This is a picture from one of my patients with herpes simplex. The presentation can change depending on the stage of the disease and the patient's response to treatment.

View attachment 34795
This is such a good post, as we are so fortunate to so frequently receive from LCT. I didn't know about the likely limitation, other than the larger surface area, of dendrites to form more peripherally. Thank you, once again, for the education. It's what makes connecting in this way so important for all of us.

I don't mean to misdirect the thread in any way, but I can't help but share a very recent case of uveitis that I initially treated with steroids.

My young partner, who is strong already and getting stronger each second, ordered all the labs for my patient looking for autoimmune disease. All negative. (And she paid all the bills yesterday too, another topic.)

Anyway, the patient developed corneal dendrites (non-central!), which, although not certain, likely indicated a preceding viral uveitic etiology.

A reminder to be on the lookout. -Charlie
 
Infectious Diseases 4th Edition 2017
Conjunctivitis, keratitis, and infections of periorbital structures

"Recurrence occurs in around 10% of cases at 1 year and 50% by 20 years. Triggers include fever, trauma, surgery and ultraviolet light. Recurrence is a consequence of latency.40 Typical presentation is central corneal dendritic ulcers without infiltration easily seen with fluoresceine test. "
 
There can be a wide range of presentations for HSV keratitis and it is also possible to have concurrent viral and bacterial infections that cause more significant disease. If in doubt there's nothing wrong with combining topical antibiotics + oral antivirals.
 
as Lloyd mentions, always check cornea sensitivity before instilling any anesthetic. If they jump out of the chair, you likely
do not have HSV.

For me they are very different presentations. HZV as well. classic HSV youll probably never miss with the bulbs etc
 
as Lloyd mentions, always check cornea sensitivity before instilling any anesthetic. If they jump out of the chair, you likely
do not have HSV.

For me they are very different presentations. HZV as well. classic HSV youll probably never miss with the bulbs etc

Would a patient with recurrent bouts of HSK no longer present primarily with symptoms of pain? -Charlie
 
Yes, the pain decreases as the nerves are damaged.
Even with the first infection a dendrite is nowhere near as painful as a bacterial ulcer. I recently saw a kid come in for “pink eye” that wasn’t getting better after a week on the maxitrol prescribed by his pediatrician. He had 12 dendrites and just complained of an irritated, red eye.
 
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Even with the first infection a dendrite is nowhere near as painful as a bacterial ulcer. I recently saw a kid come in for “pink eye” that wasn’t getting better after a week on the maxitrol prescribed by his pediatrician. He had 12 dendrites and just complained of an irritated, red eye.
Correct. That is why you check corneal sensitivity to help your diagnosis. The virus lives and reproduces in the nerves, so they are compromised from the start. It is similar to rabies.
 
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So use both?

Figure 1.
[IMG alt="Keratitis induced by HSV-1 strain H129 at 7 dpi stained with lissamine
green B (A) or rose bengal (B) ophthalmic dyes.
Lissamine green B (A) stains the large geographic lesions as
well as the punctate and dendritic lesions (arrows). Rose
bengal (B) stained the periphery of the geographic lesion
shown (bounded by arrows), but only poorly stained the
center area. Note that the corneal lesion in the rose bengal–treated
eye (B) is smaller and less conspicuous than in the
lissamine green B–treated eye (A)."]https://arvo.silverchair-cdn.com/ar...a0bw__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA[/IMG]
View OriginalDownload Slide

Keratitis induced by HSV-1 strain H129 at 7 dpi stained with lissamine green B (A) or rose bengal (B) ophthalmic dyes. Lissamine green B (A) stains the large geographic lesions as well as the punctate and dendritic lesions (arrows). Rose bengal (B) stained the periphery of the geographic lesion shown (bounded by arrows), but only poorly stained the center area. Note that the corneal lesion in the rose bengal–treated eye (B) is smaller and less conspicuous than in the lissamine green B–treated eye (A).
 
I try to remember that Herpes can look like anything. An older non-contact lens Patient with a rather nondescript epithelial lesion/ulcer - who is not a kidney Patient - would not be harmed by the Doc covering-that-base by adding some Valtrex at the same time as the topical antibiotic on an aggressive schedule [take your pick > Moxifloxacin Besivance Tobramycin]
 
Dr. Bova,

First, please let me apologize for the harsh and profane comments that I directed towards you many months ago regarding one of your posts. It was inappropriate and I will not insult you again. Also, thanks for not blocking me after my outburst.

Regarding your question, there is an excellent article in the September 2011 issue of Review of Optometry that answers practically any question you could have on this topic. It is entitled Bacterial vs. Viral: Name That Infection! and was written by Aaron Bronner, OD.

I just finished reading the piece and it is an excellent reference to learn or re-learn about the differential diagnosis of these two very different conditions.

As my friend Tom has correctly pointed out, these lesions can be similar in appearance until the clinical presentation gets worse. In other words, the pre-dendritic stage of herpes simplex is often overlooked or vague enough to create clinical confusion.

To quote from the article:

"Unfortunately, what we see more often are non-specific findings, such as injection, minimal mucous discharge, papillae or follicles (or both) and some degree of corneal infiltration, running the gamut from diffuse stromal white blood cells to a dense focal area of infiltration either with or without an overlying epithelial defect. When faced with non-specific findings, it is up to us to come to a reasonable diagnosis and form an appropriate treatment plan."

After I read the article, I was reminded of the specific regions of the cornea that play a role in the immune response to infection. In my own Review of Optometry article entitled Understanding Specular Microscopy from several years ago, I touched on the differences in endothelial anatomy between the central corneal region and the peripheral corneal region. Well, the cornea also has two distinct immunologic regions - the limbal/peripheral zone and the central zone.

The location-dependent duality of corneal immunity is the source of some fairly common differences between lesions of the periphery and lesions of the paracentral zone. For example, when the ulcer is caused by the herpes virus, if the insult is at or near the corneal periphery, the proximity to the limbus allows the immune system to more effectively contain viral activity and the characteristic dendritic appearance never develops or it may be obscured by any type of corneal infiltration.

I believe that is an important piece of information to assist in your medical decision-making.

I could go on and on, but I would simply encourage any optometrist that wants to be well-read on the question that Dr. Bova posed to just read the article and go from there...

This is a picture from one of my patients with herpes simplex. The presentation can change depending on the stage of the disease and the patient's response to treatment.

View attachment 34795
Laurence, I have no memory of your insulting me, but thanks for the apology. Your response was most informative and I will be sure to look up Sept. 2011 issue.
 
cool coincidence but just had one yesterday that didn't appear herpetic at all, just a large pool of NaFl in a generally oblong shape that I initiated q1h Besivance and then today filled in with enough epithelium to make the branches and bulbs somewhat apparent throughout

should've taken pictures and you'd have thought Dr Bova sent the patient to me ;) , how far is Uniontown from me? :)

slowed the Besivance frequence and added antiviral orals and will see how it goes

funny thing is yesterday she said she started to treat her "abrasion" with some of the bottle of drops with the brown cap she'd been given every time before but then noticed it was expired so made the appointment to see me to get a new bottle,,,, so likely this wasn't her first herpetic "abrasion"
Not very far. My location borders Ohio, WV, and Maryland.
 
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There can be a wide range of presentations for HSV keratitis and it is also possible to have concurrent viral and bacterial infections that cause more significant disease. If in doubt there's nothing wrong with combining topical antibiotics + oral antivirals.
Jeff, that what a corneal specialist told me last year.
 
the truly difficult one...fungal. difficult to diagnose sometimes. takes forever to culture. can look like anything. satellite
lesions raise the suspicion. Very difficult to treat.
 
There can be a wide range of presentations for HSV keratitis and it is also possible to have concurrent viral and bacterial infections that cause more significant disease. If in doubt there's nothing wrong with combining topical antibiotics + oral antivirals.
this is my Friday protocol when pt does not want to come back in Saturday ( ice fishing or being on the boat usually trumps stand of care for most of my pts, especially if a nice day)...honestly everytime I think pt might need to be on valtrex I just do it now..simplex or zoster...unless kidney dx
 
this is my Friday protocol when pt does not want to come back in Saturday ( ice fishing or being on the boat usually trumps stand of care for most of my pts, especially if a nice day)...honestly everytime I think pt might need to be on valtrex I just do it now..simplex or zoster...unless kidney dx
100% agree!!
 
Current apparent HSK case in office for 2 visits. 55 yo WM.

approx. 10 years ago - History of acanthamoeba ulcer and significant thinning and scarring nasally in one eye. Scar has not affected vision. Since then he had an apparent HSK bout in this eye before I came to this clinic.
He shows up a week ago with obvious dendritic (with end bulbs) ulcer formation within the limits of this scar. I start him on Famvir 250 tid.
He returned today with more diffuse staining of the dendritic lesions and the bulbs. He feels somewhat better, but is not recovering as quickly as I had expected. I wonder if the scar that the ulcer lies within is restricting the ability of the Famvir to access the affected dendritic area? I added tobradex just to help with his discomfort and to help with possible bacterial coincidental infection (as he is kind of crusty;).

Will see him at a week, and figure if he is not improving I may try Zirgan.

Any thoughts?
 
Current apparent HSK case in office for 2 visits. 55 yo WM.

approx. 10 years ago - History of acanthamoeba ulcer and significant thinning and scarring nasally in one eye. Scar has not affected vision. Since then he had an apparent HSK bout in this eye before I came to this clinic.
He shows up a week ago with obvious dendritic (with end bulbs) ulcer formation within the limits of this scar. I start him on Famvir 250 tid.
He returned today with more diffuse staining of the dendritic lesions and the bulbs. He feels somewhat better, but is not recovering as quickly as I had expected. I wonder if the scar that the ulcer lies within is restricting the ability of the Famvir to access the affected dendritic area? I added tobradex just to help with his discomfort and to help with possible bacterial coincidental infection (as he is kind of crusty;).

Will see him at a week, and figure if he is not improving I may try Zirgan.

Any thoughts?

I would have done zirgan than tobradex.
 
Not a Famvir fan for simplex..prefer big boys valtrex..like 1000 mg bid or tid. Wondering if a bigger dose of Famvir would have done the trick? Zirgan is mucho expensive
 
I'd probably culture this one. if they walk in and hand you a red flag, accept it, and proceed accordingly.
 
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Thanks, I'll see where he is on the other side of the weekend. I figure at least he will feel a little better. LOL.
 
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Dr. Bova,

First, please let me apologize for the harsh and profane comments that I directed towards you many months ago regarding one of your posts. It was inappropriate and I will not insult you again. Also, thanks for not blocking me after my outburst.

Regarding your question, there is an excellent article in the September 2011 issue of Review of Optometry that answers practically any question you could have on this topic. It is entitled Bacterial vs. Viral: Name That Infection! and was written by Aaron Bronner, OD.

I just finished reading the piece and it is an excellent reference to learn or re-learn about the differential diagnosis of these two very different conditions.

As my friend Tom has correctly pointed out, these lesions can be similar in appearance until the clinical presentation gets worse. In other words, the pre-dendritic stage of herpes simplex is often overlooked or vague enough to create clinical confusion.

To quote from the article:

"Unfortunately, what we see more often are non-specific findings, such as injection, minimal mucous discharge, papillae or follicles (or both) and some degree of corneal infiltration, running the gamut from diffuse stromal white blood cells to a dense focal area of infiltration either with or without an overlying epithelial defect. When faced with non-specific findings, it is up to us to come to a reasonable diagnosis and form an appropriate treatment plan."

After I read the article, I was reminded of the specific regions of the cornea that play a role in the immune response to infection. In my own Review of Optometry article entitled Understanding Specular Microscopy from several years ago, I touched on the differences in endothelial anatomy between the central corneal region and the peripheral corneal region. Well, the cornea also has two distinct immunologic regions - the limbal/peripheral zone and the central zone.

The location-dependent duality of corneal immunity is the source of some fairly common differences between lesions of the periphery and lesions of the paracentral zone. For example, when the ulcer is caused by the herpes virus, if the insult is at or near the corneal periphery, the proximity to the limbus allows the immune system to more effectively contain viral activity and the characteristic dendritic appearance never develops or it may be obscured by any type of corneal infiltration.

I believe that is an important piece of information to assist in your medical decision-making.

I could go on and on, but I would simply encourage any optometrist that wants to be well-read on the question that Dr. Bova posed to just read the article and go from there...

This is a picture from one of my patients with herpes simplex. The presentation can change depending on the stage of the disease and the patient's response to treatment.
Dr Thomas,
Could you post a link to the article you wrote?
Thank you
 
Found it in case Dr. Thomas doesn't see this:

Use Specular Microscopy to Diagnose Corneal Disease​

Specular microscopy is a noninvasive photographic technique that facilitates rapid and accurate diagnosis of corneal endotheliopathies.​

Craig Thomas, O.D.



Corneal endotheliopathy is a broad term used to classify several diseases and clinical circumstances that affect the structure and function of the corneal endothelium. Because the endothelium is responsible for maintaining proper corneal hydration, clinically significant corneal endotheliopathies can lead to edema and a loss of transparency.1

1. Factors that can compromise the corneal endothelium and cause corneal edema.3
Common ocular conditions, such as glaucoma, uveitis and Fuchs endothelial dystrophy, may produce changes in the structure and function of the corneal endothelium that result in corneal edema and visual impairment. Additionally, clinical circumstances, such as contact lens wear and intraocular surgery, may compromise the endothelium and cause corneal edema (figure 1). An accurate diagnosis of endothelial disease may be the key in not only determining cause of corneal edema, but also developing a treatment plan.

2. Specular photomicrograph of a normal corneal endothelium in a 21-year-old female patient.
Specular microscopy is a noninvasive photographic technique that allows you to visualize and analyze the corneal endothelium. Using computer-assisted morphometry, modern specular microscopes analyze the size, shape and population of the endothelial cells. The instrument projects light onto the cornea and captures the image that is reflected from the optical interface between the corneal endothelium and the aqueous humor. The reflected image is analyzed by the instrument and displayed as a specular photomicrograph (figure 2). In clinical practice, specular microscopy is the most accurate way to examine the corneal endothelium.

The Corneal Endothelium
The corneal endothelium is a monolayer of 350,000 to 500,000 specialized cells that cover the posterior surface of the cornea. One of the endotheliums physiological functions is to secrete a collagen matrix that forms Descemets membrane.1 But, the primary physiological function of the corneal endothelium is to maintain the health and transparency of the corneal stroma. Because the cornea is avascular, the supply of nutrients occurs via diffusion of glucose and other solutes from the anterior chamber across the cornea endothelium. To facilitate diffusion, intraocular pressure constantly forces aqueous into the stroma from the anterior chamber. Although the influx of aqueous into the stroma is necessary to maintain corneal health, the level of corneal hydration must be controlled to prevent edema.

Biomechanical properties of the cornea. Corneal hydration is one of the biomechanical properties of the anterior segment, and it is affected by several interdependent factors.2 To control corneal hydration, the endothelium forms an anatomical and physiological barrier to the aqueous that makes the structure semi-permeable.

Fluid barrier function.
Endothelial permeability is controlled by tight junctions that are formed between endothelial cells. These connections between the cells are found at the apex of the lateral cell membrane and serve to restrict the amount of fluid entering the corneal stroma.3

Metabolic pump function.
In addition to its barrier function, the endothelium also maintains stromal deturgescence by pumping fluid out of the stroma through an active transport mechanism. The site of the metabolic pump is also within the lateral cell membrane, and it is a part of a completely formed junctional complex between the endothelial cells. The active transport pumping mechanism uses enzymes to translocate bicarbonate ions across the endothelial cell membrane, which passively permits water to follow the ions into the anterior chamber.4

Normal Corneal Endothelium
With specular microscopy, the corneal endothelium appears as a somewhat-regular array of cellsthe endothelial mosaic. In this mosaic configuration, all of the endothelial cells appear to be approximately the same size and shape.5

Stability of the endothelial mosaic. In a normal endothelium, more than 60% of the endothelial cells are six-sided. The size and shape of the endothelial cells is important because adjacent cells with similar dimensions best maintain the fluid barrier function of the endothelium.6

Rate of polymegethism. Complete coverage of the posterior corneal surface is required to maintain the barrier function and the active transport mechanism of the corneal endothelium. Because of normal attrition, the central cornea loses 100 to 500 endothelial cells per year. When these cells die, they slough off the posterior surface of the cornea into the anterior chamber, creating a gap in the endothelial mosaic that compromises both the barrier and pump functions of the endothelium.

To repair the gap, the endothelium relies on cellular migration and cellular fusion.3 In this wound repair mechanism, the endothelial cells adjacent to the defect move to fill in the space vacated by the sloughed cell. The endothelial cells either stretch and slide into a different position, or they fuse together to re-establish complete coverage of the posterior surface of the cornea.3 This movement of the endothelial cells creates a variation in cell size known as polymegethism.

Because polymegethism is a reflection of the normal endothelial cell movement that characterizes the wound repair mechanism, there is always some degree of polymegethism in the corneal endothelium. The rate of polymegethism is represented by the coefficient of variation (CV). CV values measured between 0.22 and 0.31 are considered normal.7

Endothelial cell density. Maintaining both the barrier and pump function requires a certain number of endothelial cells to cover the posterior surface of the cornea. The minimum number of cells, or critical cell density, averages between 300 and 500 cells/mm2.4,8

The central corneal endothelium changes as a person ages. From age 20 to 50, the endothelial cell density remains relatively stable for most people. Beyond age 50, a slow decline begins. By age 60, most people experience a significant reduction in endothelial cell density (see Endothelial Cell Density by Age).3,5,9

Endothelial Cell Density by Age
Age Average Endothelial
Cell Density (cells/mm2)
10 - 192,900 - 3,500
20 - 292,600 - 3,400
30 - 392,400 - 3,200
40 - 492,300 - 3,100
50 - 592,100 - 2,900
60 - 692,000 - 2,800
70 - 791,800 - 2,600
80 - 891,500 - 2,300
Abnormal Corneal Endothelium
Using specular microscopy, endothelial disease may be characterized by one or more abnormalities of cell morphology.

Presence of pleomorphism. Pleomorphism is a significant disruption in the regular hexagonal pattern of the endothelium that causes a decrease in endothelial mosaic stability. Pleomorphism occurs secondary to physiological stress from ocular disease, contact lens wear or normal aging changes.4,6,7

If a patients corneal endothelium demonstrates less than 50% hexagonally-shaped cells, he or she is considered to have clinically significant pleomorphism. Because of its effect on the fluid barrier function of the endothelium, the presence of pleomorphism increases the patients risk of developing iatrogenic corneal endotheliopathy and postoperative corneal edema.5

Elevated or abnormal rate of polymegethism. An elevated or abnormal rate of polymegethism is usually the first sign of endothelial disease. This finding indicates physiological stress to the corneal endothelium and an overactive wound repair mechanism. CV values from 0.32 to 0.40 are elevated, and CV values above 0.40 are abnormal. Although endothelial function may still be adequate in these corneas, the endothelium may be more susceptible to additional trauma from insults, such as intraocular surgery, glaucoma, diabetes, uveitis or contact lens wear.5

Abnormal reduction in endothelial cell density. Advanced age, disease and injury may produce significant reductions in endothelial cell density. When present, endothelial cell loss should be bilaterally symmetrical; a difference of more than 280 cells/mm2 is clinically significant.5

3. Transmission electron micrograph of corneal guttata. Endothelial cells wrap around and cover the corneal guttata to maintain complete coverage of the posterior corneal surface.3
The appearance, enlargement or coalescence of corneal guttata. Corneal guttata are secretions of collagen from the endothelial cells that form a nodularity on the posterior surface of Descemets membrane (figure 3). These nodules are created when endothelial cells under physiological stress secrete an altered basement membrane material that accumulates under the cells. The deposits of abnormal collagen eventually form a nodular-shaped lesion called a corneal gutta.

Corneal Endotheliopathies
Corneal endotheliopathies are classified as primary or secondary. In primary corneal endotheliopathies, endothelial damage is not associated with any other ocular or systemic disorder. In secondary corneal endotheliopathies, there is a recognizable ocular or systemic disorder that contributes to the loss of endothelial cell structure and function. Examples of secondary endotheliopathies include contact lens-induced endotheliopathy, iatrogenic endotheliopathy and corneal endotheliopathy secondary to ocular inflammation.1

Corneal guttata. Corneal guttata are the most common primary corneal endotheliopathy. The clinical finding of corneal guttata is not specific; they may occur as part of the normal aging process, in corneal endothelial dystrophies, or secondary to ocular inflammation and trauma. Corneal guttata mainly affect the central region of the cornea and, when mild or moderate in presentation, they usually have no effect on visual acuity.10 They are present in 70% of the population over 40 years old.11

4. Corneal guttata visualized during a biomicroscopic examination.
Corneal guttata can be visualized during biomicroscopy with the specular reflection illumination technique (figure 4). Under specular microscopy, a corneal gutta appears as a darkened area that resembles a hole in the endothelial mosaic (figure 5). The darkened area is created on the specular photomicrograph because the apex of the corneal gutta lies outside the specular reflections plane of focus.12

5. Specular photomicrograph of a corneal gutta.
The natural history of corneal guttata progression includes five specific stages of development, which can be discerned with specular microscopy. In stage 1, the gutta nodule appears as a small, dark structure in the center of an endothelial cell. In stage 2, the gutta nodule is almost the same size as an endothelial cell and the surrounding cells have a stretched appearance. In stage 3, the gutta is very large and many endothelial cells are involved with one nodule. Also, endothelial cells that are adjacent to large gutta have missing cell boundaries, and multiple guttae may be present. In stage 4, the individual gutta have coalesced and the endothelial cells between the guttata have become abnormal. In stage 5, progressive coalescence of corneal guttata continues, making the normal tessellation of the endothelial mosaic difficult or impossible to visualize.13

6. Confluent corneal guttata in Fuchs endothelial dystrophy.
Fuchs endothelial dystrophy. When confluent corneal guttata are present with clinically significant corneal edema, the condition is called Fuchs endothelial dystrophy (figure 6). This disease affects 4% of the population over 40 years old and is characterized by a progressive loss of endothelial cell structure and function. It eventually leads to corneal edema and a loss of corneal transparency.14

Age-related endotheliopathy. Advancing age may produce abnormal or asymmetric reductions in endothelial cell density, an abnormal increase in the rate of polymegethism, clinically significant pleomorphism and/or an increase in the development of corneal guttata.5

Iatrogenic endotheliopathy. Surgical trauma during normal cataract surgery generally results in a 4% to 10% loss of endothelial cells. This postoperative cell loss is called iatrogenic endotheliopathy. In addition to the immediate cell loss associated with the procedure, cataract surgery also produces an accelerated rate of endothelial cell loss for at least 10 years after surgery. When too many cells are lost from iatrogenic endotheliopathy, endothelial function is compromised and postoperative corneal edema develops.1,4,7,15

Risk factors for the development of clinically significant iatrogenic endotheliopathy and postoperative corneal edema include previous ocular surgery, diabetes, glaucoma, previous ocular inflammation, an abnormal rate of polymegethism, the presence of pleomorphism, the presence of severe corneal guttata and Fuchs endothelial dystrophy.5,6,8,11 In patients with clinically significant iatrogenic endotheliopathy, specular microscopy reveals large reductions in endothelial cell density that occur over short periods of time.

7. Endothelium of a 55-year-old woman with a 30-year history of PMMA and gas-permeable contact lens wear. Note the abnormal rate of polymegethism, the presence of pleomorphism, the abnormal reduction in cell density and the presence of stages 1-3 corneal guttata.
Contact lens-induced endotheliopathy. Contact lens wear produces both acute and chronic morphologic changes in the corneal endothelium. Specifically, both the presence and rate of clinically significant polymegethism increases as the span of contact lens wear increases (figure 7).1,5-7,16,17

Although several mechanisms contribute to the development of contact lens-induced endotheliopathy, wearing contact lenses with low oxygen permeability appears to be the primary cause. Also, contact lens-induced hypoxia can produce endothelial cell damage and a loss of endothelial function secondary to chronic corneal swelling and de-swelling.5,6,16,17

When patients develop contact lens-induced endotheliopathy, discontinuing contact lens wear does not produce a rapid reversal of the morphologic changes. However, some degree of recovery is possible over several years if contact lens wear is discontinued, or if the patient switches to a contact lens with a significantly higher degree of oxygen permeability.6,7,16,17

As with all types of corneal endotheliopathy, contact lens induced-endotheliopathy may produce the clinical signs and symptoms associated with corneal edema. In addition to blurred vision, fluctuating vision and photophobia, contact lens wearers with clinically significant contact lens-induced endotheliopathy may complain of foreign body sensation when wearing their contact lenses, or corneal exhaustion syndrome in severe cases.6

Endotheliopathy secondary to ocular inflammation. Iridocyclitis can result in endothelial cell loss and reduced endothelial cell function.4 Specifically, iridocyclitis causes a release of immune response proteins into the anterior chamber that leads to endothelial cell death.18

8. Endothelium of a patient with acute anterior uveitis. Note the numerous dark structures and the dislodged endothelial cells in the center of the image.
Also, during an acute inflammatory episode, mononuclear inflammatory cells can penetrate the tight junctions between the endothelial cells and insert themselves between the endothelium and Descemets membrane. This can cause individual endothelial cells to dislodge and float free in the aqueous.5,17 In acute anterior uveitis, specular microscopy may reveal several well-demarcated dark structures usually located at endothelial cell intersections that are thought to be invading white blood cells (figure 8).5

Glaucoma-induced endotheliopathy. Long-term exposure to elevated intraocular pressure can produce an abnormal reduction in endothelial cell density. One study suggested that the mechanism of cell loss is not the result of increased intraocular pressure, but rather some other physiological alteration in the glaucomatous eye, such as abnormal aqueous outflow or decreased oxygen concentration in the aqueous.5

Treatment Options
Although no medical treatment can promote endothelial wound healing or endothelial cell regeneration, there are several treatment options for your patients with clinically significant corneal endotheliopathies. In any given case, you must treat each specific endotheliopathy differently.

For example, discontinuation of contact lens wear is a conservative medical treatment for patients with contact lens-induced endotheliopathy. Or, an active medical treatment may involve continuing contact lens wear by prescribing different contact lenses with higher oxygen permeability.

In patients with Fuchs endothelial dystrophy, palliative medical treatment may involve prescribing a topical hyperosmotic solution or ointment. However, a more active approach might consist of surgical procedures, such as deep lamellar endothelial keratoplasty or penetrating keratoplasty.19

In patients with ocular inflammation, prophylactic medical treatment of a secondary endotheliopathy may involve the aggressive use of topical steroids instead of allowing the inflammation to resolve on its own.4

Regardless of the type of corneal endotheliopathy or how you elect to administer medical treatment, your ultimate goals are to prevent, reduce or eliminate corneal edema, maintain corneal transparency, and maintain the endothelial functional reserve.

Specular microscopy helps facilitate treatment by allowing you to diagnose any type of corneal endotheliopathy earlier and more accurately. Because the technology reveals information about the endothelium that is either difficult or impossible to derive from the clinical examination alone, specular microscopy helps you provide the best corneal care possible.
Dr. Thomas is in private practice in Dallas and is an adjunct assistant professor at the University of Houston College of Optometry. He is also a paid consultant for Konan Medical, Inc.

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