Periocular Skin Research Articles

On the essential involvement of neutrophils in the immunopathologic disease: herpetic stromal keratitis.

Corneal infection with herpes simplex virus-1 in immunocompetent mice induces an immunopathologic response termed herpetic stromal keratitis (HSK). The earliest sign of disease is neutrophil infiltration, which lasts for 48 to 72 h and then disappears. However, a secondary neutrophil infiltration, this time more massive, occurs, beginning 8 to 9 days postinfection, a time in which HSK becomes clinically evident. The role of neutrophils in HSK expression was investigated by eliminating such cells using a specific mAb (RB6-8C5). In neutrophil-depleted immunocompetent mice, virus replicated more abundantly, but no effects on HSK expression were observed, possibly because sustained neutropenia could not be maintained. However, using a severe combined immunodeficient mouse model, in which HSK does not occur unless given adoptive transfer of CD4+ T cells, the effects of neutrophil depletion were more pronounced. There were significantly less incidence and severity of HSK in CD4+ T cell-reconstituted severe combined immunodeficient mice that were depleted of neutrophils as compared with controls. Neutrophil-depleted mice displayed moderate to severe periocular skin lesions, progressively became cachetic, and developed signs of encephalitis. Virus was recovered at higher titers and for longer periods from eyes of neutrophil-depleted animals. Brain virus titers were also significantly higher on day 12 postinfection as compared with control animals. These results suggest that herpes simplex virus infection of the cornea rapidly invokes recruitment of neutrophils that may aid in viral clearance, and that neutrophils directly or indirectly serve as agonists in perpetuating a CD4+ T cell-mediated inflammatory reaction.

Periocular skin reshaping by CO2 laser coagulation

When blepharoplasty is performed by transconjunctival route, sometimes the excess of skin created by overlaxness of the lower lid does not retract to achieve the desired cosmetic result. We propose a method for controlled retraction of the eyelid by coagulating the skin using the CO2 laser. Thanks to this approach, the lower eyelid's tone recovers and the desired cosmetic appearance is achieved. Results of 37 patients that were treated by 10 W CO2 laser, 5-mm defocused beam diameter, and pulses of 100 ms, are presented. Follow-up shows that periocular skin reshaping by CO2 laser for laxened eyelid is a safe method and it can be considered a good alternative of treatment for blepharochalasis without skin excision.

Porcelinizing Discolorization of the Periocular Skin Following Botulinum A Toxin Injections

Porcelinizing Discolorization of the Periocular Skin Following Botulinum A Toxin Injections

Inflammatory infiltration of the trigeminal ganglion after herpes simplex virus type 1 corneal infection.

Following herpes simplex virus type 1 (HSV-1) infection of the cornea, the virus is transmitted to the trigeminal ganglion, where a brief period of virus replication is followed by establishment of a latent infection in neurons. A possible role of the immune system in regulating virus replication and maintaining latency in the sensory neurons has been suggested. We have investigated the phenotype and cytokine pattern of cells that infiltrate the A/J mouse trigeminal ganglion at various times after HSV-1 corneal infection. HSV antigen expression in the trigeminal ganglion (indicative of the viral lytic cycle) increased until day 3 postinfection (p.i.) and then diminished to undetectable levels by day 7 p.i. The period of declining HSV antigen expression. was associated with a marked increase in Mac-1+ cells. These cells did not appear to coexpress the F4/80+ (macrophage) or the CD8+ (T cell) markers, and none showed polymorphonuclear leukocyte morphology, suggesting a possible early infiltration of natural killer cells. There was also a significant increase in the trigeminal ganglion of cells expressing the gamma delta T-cell receptor, and these cells were found almost exclusively in very close association with neurons. This period was also characterized by a rapid and equivalent increase in cells expressing gamma interferon and interleukin-4. The density of the inflammatory infiltrate in the trigeminal ganglion increased until days 12 to 21 p.i., when it was predominated by CD8+, Mac-1+, and tumor necrosis factor-expressing cells, which surrounded many neurons. By day 92 p.i., the inflammatory infiltrate diminished but was heaviest in mice with active periocular skin disease. Our data are consistent with the notion that gamma interferon produced by natural killer cells and/or gamma delta T cells may play an important role in limiting HSV-1 replication in the trigeminal ganglion during the acute stage of infection. In addition, tumor necrosis factor produced by CD8+ T cells and macrophages may function to maintain the virus in a latent state.

Periocular Skin Reshaping by CO2 Laser Coagulation

Periocular Skin Reshaping by CO2 Laser Coagulation

Characterization of herpes simplex virus type-1 infection and herpetic stromal keratitis development in IFN-gamma knockout mice.

Herpetic stromal keratitis (HSK) has an immune-mediated pathogenesis that involves T cells that have a type 1 cytokine profile. IFN-gamma is suspected to be the type 1 cytokine involved in ocular pathology, and to test this notion more directly the pathogenesis of HSK was compared in mice deficient in the IFN-gamma gene (gamma knockout or gko) and control mice (wild-type littermates or BALB/c mice). The clinical course of HSK in gko mice closely paralleled that in control mice, yet virus persisted in the corneas of gko mice for an extended period of time, severe periocular skin lesions developed, and gko mice were far more susceptible to encephalitis. Delayed-type hypersensitivity to viral Ag was present, though diminished, in knockout mice, and serum herpes simplex virus-specific IgG isotypes indicated a Th2 shift. No differences existed in proliferative responses to in vitro Ag stimulation in gko vs control mice nor in T cell or proinflammatory cytokine mRNA levels in the corneas of infected mice. However, up-regulation of Th2 cytokine mRNA did occur in in vitro Ag-stimulated gko immune splenocytes. Histopathologic lesions were not statistically different between any of the groups of mice analyzed. These observations indicate that although IFN-gamma plays an important role in the clearance of virus from the eye, the pathogenesis of HSK lesions most likely involves additional cytokines, inflammatory mechanisms, or immune responses to nonviral Ags.

Cryotherapy for eyelid and periocular basal cell carcinomas: outcome in 166 cases over an 8-year period.

Basal cell carcinoma (BCC) is the most common of all malignant tumours and often appears on the periocular skin. In the present study, patients with 166 eyelid and periocular BCCs were treated with cryotherapy at the Eye Clinic of the Kuopio University Hospital. Seven patients with a total of eight BCCs died during the first year after cryotherapy, of causes unrelated to BCC. These cases were excluded from the analysis of outcome. The tumours were photographed before excisional biopsy and histopathological examination. The BCCs were frozen twice with liquid nitrogen in a closed cryoprobe; a tissue thermometer was used. During the mean follow-up of 5 years for 158 BCCs, recurrences were observed in 12 cases (7.6%). The most important prognostic factors for recurrence were large tumour size (maximum diameter exceeding 10 mm), tumour extension into the lid margin, and cicatrising (morpheaform) BCC. The complications of cryotherapy were slight, but in some cases lid ectropion needed surgical correction. The functional and cosmetic results were very satisfactory in most cases. Ninety-two percent of BBCs treated with cryotherapy did not recur during mean follow-up of 5.0 years (range 1.6-8.4 years).

Involvement of LFA-1 and ICAM-1 in the herpetic disease resulting from HSV-1 corneal infection

Herpes simplex virus type 1 (HSV-1) corneal infection in immunologically normal mice results in a transient epithelial lesion followed in about 2 weeks by a potentially blinding inflammatory response in the corneal stroma, and a mild blepharitis. Similarly infected T cell-deficient mice do not develop corneal stromal inflammation, but exhibit severe periocular skin disease and succumb to viral encephalitis. The role of certain adhesion molecules in both T cell activation, and in the extravasation of inflammatory cells from the blood into inflammatory sites is now being established. These studies investigated the involvement of the adhesion pair LFA-1/ICAM-1 in the disease that results from HSV-1 corneal infection in mice. Treatment of mice with mAb to LFA-1 beginning 1 day before HSV-1 corneal infection resulted in a delay in the onset of stromal inflammation, but ultimately stromal inflammation developed to a normal extent. This treatment also caused a significant exacerbation of periocular skin disease, but did not render mice susceptible to encephalitis. Treatment with mAb to ICAM-1 beginning 1 day before HSV-1 corneal infection caused an acceleration of both stromal inflammation and periocular skin disease, and rendered mice uniformly susceptible to lethal encephalitis. Treatment with either mAb beginning 6 days after HSV-1 corneal infection did not significantly affect the clinical course of herpetic disease. Our findings suggest that LFA-1 may play a role in the early phase of corneal stromal inflammation following HSV-1 corneal infection. Both LFA-1 and ICAM-1 appear to be important for protection of the skin from HSV-1 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

The family of sunlight-related eye diseases.

Five ocular disorders, independent clinical entities affecting different parts of the eye with distinctive histopathological features, are part of the same family of eye diseases because they share the same causal factors, of which the most important is molecular damage produced by sunlight. This family of eye diseases includes the major sources of impaired vision and blindness in our society, age-related cataract and age-related macular degeneration. Pterygium, photokeratitis, and cancer of peri-ocular skin are also sunlight-related eye diseases. In each condition, solar radiation, oxygen, and heat, acting in combination, are the primary causal factors. Analysis of the action spectra indicates that only the high-energy radiation in the solar spectrum, particularly the ultraviolet (UV), is hazardous to the eye. The evidence in support of these conclusions is summarized. It indicates that the risk of all sunlight-related eye diseases can be diminished by use of eyewear that absorbs the high-energy constituents of solar radiation during exposure to sunlight.

The red face in domestic animals

Red face in veterinary dermatology means essentially facial erythema. Because the skin can be variously pigmented and is naturally covered by hair, it may be difficult to ascertain the presence of redness. Light-colored hair and depigmented skin may help the clinician recognize a so-called “red face.” In the majority of cases, however, erythema is easily identified, even in dark-skinned animals, because it is associated with alopecia. The absence of hair reveals the redness of the skin surface. Alopecia is frequently self-induced as a result of pruritus. Animals with facial pruritus rub their faces on rough surfaces. Dogs and cats can scratch off the hair with the rear legs and, sometimes, also with the forelegs. Pruritus can be related to a great variety of pathologic conditions. In these cases, erythema is not primary but is related to self-trauma as well as alopecia. On the other hand, in a few cases, pruritus may be secondary to the erythema and directly caused by the primary etiology. The facial redness of domestic animals is not usually uniform. Areas commonly involved are the internal surface of the pinna, the dorsum of the nose, and the perioral and periocular skin. This is related not only to the variety of causes but also to the anatomic differences between humans and animals. Animals do not have facial areas analogous to either the cheeks or the forehead, which are the largest areas on the human face. In veterinary dermatology, “red muzzle” is probably a less frequently used term compared with “red face” in human medicine. In domestic animals, red face is more commonly associated with immune-mediated and parasitic skin diseases.

IFN-gamma and IL-2 are protective in the skin but pathologic in the corneas of HSV-1-infected mice.

HSV type 1 (HSV-1) infection of the mouse cornea results in a tissue-destructive inflammatory reaction in the cornea, but little or no disease in the skin surrounding the eye. Depleting T lymphocytes from mice before HSV-1 corneal infection prevents the corneal inflammation but severely exacerbates the periocular skin lesions. Studies described in this communication investigated the role of T cell cytokines in the corneal and periocular skin disease induced by HSV-1 corneal infection. Mice received weekly i.p. injections of rat mAb specific for IL-2, IL-4, or IFN-gamma beginning 1 day before (day -1) or 6 days after (day +6) corneal infection with the RE strain of HSV-1. The severity of corneal inflammation and the area of periocular skin involvement were measured. Treatment with anti-IFN-gamma or anti-IL-2 significantly reduced the incidence and severity of corneal inflammation. Treatment was equally effective when initiated on day -1 (before T cell activation) or day +6 (after T cell activation but before the initiation of corneal inflammation). Treatment with anti-IL-4 had no effect. The histologic features of corneal inflammation in mock-treated mice included neovascularization, corneal edema, and cellular infiltration. Corneas of anti-IL-2-treated mice that developed inflammation had similar but less severe histologic features. Corneas of anti-IFN-gamma-treated mice that developed inflammation had neovascularization and edema but minimal cellular infiltration. Treatment with anti-IFN-gamma or anti-IL-2 significantly exacerbated periocular skin lesions when initiated at day -1, but not when initiated at day +6. Anti-IL-4 treatment had no effect on skin lesions. Treatment with either anti-IFN-gamma or anti-IL-2, when initiated at day -1, significantly inhibited the delayed-type hypersensitivity response to HSV Ag, but when treatment was begun at day +6 only anti-IFN-gamma significantly inhibited the delayed-type hypersensitivity response. Our findings suggest that IFN-gamma and IL-2 are important elements in both an immunopathologic T-lymphocyte response to HSV-1 Ag in the cornea and a protective T lymphocyte response in the skin.

Varied Clinical Spectrum of Necrobiotic Xanthogranuloma

Four cases are presented that illustrate a wide spectrum of ophthalmologic and systemic features of necrobiotic xanthogranuloma (NXG). Case 1 initially had signs of Cogan syndrome, and then developed chronic lymphocytic leukemia. Case 2, the first case of NXG to undergo autopsy, had progressive cicatricial lid retraction and corneal perforation. Case 3 had a more typical presentation of diplopia and blepharoptosis caused by orbital and periorbital infiltrative masses. Case 4 had nondeforming periocular skin lesions over a 6-year period. In all four cases, the diagnosis was made on the basis of characteristic histopathologic and laboratory findings. Although the cause of NXG is still obscure, in many cases it appears to be a forerunner of lymphoproliferative diseases.

Concurrent regeneration of T lymphocytes and susceptibility to HSV-1 corneal stromal disease

In these studies, mice were simultaneously depleted of CD4 and CD8 T lymphocytes (T cell-depleted) by weekly intraperitoneal injections of rat monoclonal antibodies specific for L3T4 and Lyt-2 respectively, beginning 1 day before topical corneal infection with KOS herpes simplex virus type 1 (HSV-1). Control mice were mock-depleted by weekly injections of saline. All mice developed dendritic epithelial lesions 2-3 days after infection, which healed within 2 days. Fifty percent of the mock-depleted mice developed severe HSV-1 stromal disease, which began 9-14 days after infection. No skin lesions were observed in mock-depleted mice. In contrast, none of the T cell-depleted mice developed HSV-1 corneal stromal disease through an initial 30 day observation period. These mice did develop severe periocular skin lesions. After 30 days, the T cell-depleted mice were subdivided into two groups. In one group, T cell depletion was continued and the mice remained largely free of stromal disease for an additional 30 days (one of 30 mice developed a mild stromal haze). T cell depletion was discontinued in the second group. During the subsequent 30 days the CD4 and CD8 T cells in their lymph nodes and spleens recovered to approximately 50% of normal, and 43% (13 of 30) of the mice developed severe HSV-1 stromal disease. The skin lesions healed in all T cell-depleted mice between days 30 and 60, even when T cell depletion was maintained. Our findings demonstrate that T cells are both protective (preventing the spread of HSV-1 in the skin) and detrimental (inducing the destruction of the corneal stroma).(ABSTRACT TRUNCATED AT 250 WORDS)

Punch Biopsy Technique for the Ophthalmologist

To the Editor. —The ophthalmologist is often confronted with a patient having a periocular or facial skin lesion that is suspected of being malignant. The proper management of these lesions requires a biopsy and histopathologic examination. An incisional biopsy can be easily accomplished with a punch biopsy technique that is widely used by our dermatology colleagues. The ease of obtaining a good specimen, the uniform nature of the tissue obtained, and the simplicity of wound closure lends itself to use in the ophthalmologist's office. Disposable punches come in various sizes, ranging from 1 mm to 10 mm in diameter (Fig 1). The 3-mm or 4-mm punch is best suited for periocular or facial lesions. The punch biopsy is performed after intradermal or subcutaneous injection of local anesthesia and proper skin preparation with povidone-iodine (Betadine) solution. The punch is placed perpendicular to the lesion and gentle vertical pressure combined with a

Treatment of Periocular Tumours of Horses using Radioactive Gold198 Grains

The literature is briefly reviewed concerning the clinical features of equine cutaneous tumours. The data from 19 horses with periocular skin tumours are reported together with the results of their treatment by implantation with radioactive gold198. The principles governing the implantation of radioactive sources are explained and a method for computing the initial activity of the sources is outlined. Five histologically different tumour types were treated in this series of 19 horses, 2 horses were bilaterally affected. The techniques of implantation using a simple needle/stillette combination and a purpose built gold grain implantation gun are described and the postoperative course of the animals is traced. The treatment was successful in ablating the tumour mass and preventing regrowth in 19 of 21 periocular tumour groups. The cosmetic effects of the treatment were found to be satisfactory. Emphasis is laid on the care needed in handling the radioactive material and on the need for a thorough understanding of the principles involved in radiotherapy. Doses received by the operator during an implantation procedure are quoted which show that the technique is safe as well as being effective.

Efficacy, simplicity, and safety of X-ray therapy of basal-cell carcinomas on periocular skin.

X-ray therapy of basal-cell carcinomas of periocular skin is highly successful, easy to carry out, safe, and attended by cosmetic results that are good to excellent.

A study of the periocular projections towards the frontal cortex in Papio papio

A study of the cortical projections from the periocular and facial skin was carried out on photosensitive and non-photosensitive baboons ( Papio papio). (In a photosensitive Papio papio, intermittent light stimulation at 25/sec induces myoclonus and EEG signs of epilepsy.) These projections were demonstrated by using subcutaneous electrical stimuli and recording at the cortical level with bipolar and monopolar surface electrodes, or concentric intracortical electrodes, or tungsten micro-electrodes. Various experimental situations were used, the animals being either awake in a restraining chair or immobilized with gallamine and local analgesia. The periocular afferents project to a large cortical territory, including the parietal cortex and a large part of the frontal lobe, occupying almost the whole of areas 4 and 6. Responses of maximal amplitude were observed in the region of the precentral sulcus. The latencies of the responses in the frontal area were longer than in the parietal area; however, intracortical records exclude the possibility that these frontal responses were due to simple diffusion from the specific territory, in particular because ablation of the specific area for the face did not suppress frontal responses to periocular stimulation. Finally, it was found that the responses occurring in area 16 to stimulation of the ipsilateral superciliary arch were always larger in amplitude than those obtained to contralateral stimulation. This feature distinguishes the frontral projections derived from the periocular zone from those derived from the limbs; it is not yet possible to conclude wether these projections are involved or not in the facilitation of photic epilepsy through tactile stimulation of the periocular zone of Papio papio (as observed previously).