Pilocarpine 1.25% and the changing landscape of presbyopia treatment.

PURPOSE OF REVIEW: Despite affecting approximately 1.8 billion individuals worldwide, until recently, a pharmacologic treatment for presbyopia was not available. This special commentary reviews the treatment of presbyopia with a focus on the recently approved medication Vuity (pilocarpine 1.25%, Allergan, an AbbVie Company). RECENT FINDINGS: Vuity is a re-engineered formulation of pilocarpine 1.25% specifically designed for the treatment of presbyopia. Recently published results from the GEMINI 1 Phase 3 clinical trial reported improvement in distance corrected near vision without significant compromise in distance vision. No unexpected safety findings were reported with mild headache being the most common adverse event. Notably, there were no reported cases of retinal detachment or angle closure during the 30-day phase 3 clinical trials. SUMMARY: Vuity is the first treatment designed and FDA approved to treat the growing presbyopia market. Phase 3 clinical trials demonstrated its ability to improve near vision without significant compromise in distance vision. We recognize this paradigm shift in the treatment of presbyopia and anxiously await additional treatment options for this ubiquitous condition.

Actinic Granuloma of the Conjunctiva: Case Series and Review of the Literature.

PURPOSE: To characterize the clinical and histopathologic features of actinic granuloma of the conjunctiva. DESIGN: Retrospective observational case series METHODS: Institutional pathology records between 2014 and 2020 were searched for all cases of conjunctival actinic granuloma. Information collected included age, sex, ocular and medical history, clinical findings, laboratory workup, treatment, follow-up, pathologic diagnosis, and histopathologic inflammation pattern. RESULTS: Eight eyes of 8 patients, 5 men and 3 women, with a median age of 43 years (mean 49, range 24-83) were identified. Clinical diagnosis was pterygium (n = 4, 50%), inflamed pterygium (n = 1, 13%), pterygium vs conjunctival squamous cell carcinoma (n = 1, 13%), episcleritis vs inflamed pinguecula (n = 1, 13%), and scleritis vs keratoacanthoma (n = 1, 13%). Of 5 lesions with follow-up information, none recurred following excision with a median follow-up of 9 weeks (mean 19 weeks, range 1-61 weeks). Allergy/atopy was documented in 4 of 7 (57%) patients with available medical information. There were no other systemic associations. Histopathologically, actinic granuloma was associated with pterygium (n = 6, 75%) and pinguecula (n = 2, 25%). All lesions were composed predominantly of histiocytes and a variable number of foreign body-type giant cells associated with a focus of severe actinic elastosis. The inflammatory pattern was giant cell (n = 4, 50%), sarcoidal (n = 2, 25%), histiocytic (n = 1, 13%), and combined histiocytic and sarcoidal (n = 1, 13%). CONCLUSION: Conjunctival actinic granuloma has diverse clinical and histopathologic manifestations, which need to be distinguished from other autoimmune, neoplastic, and infectious etiologies. This lesion frequently occurs in pre-existing pterygium and pinguecula and may be associated with allergy and atopy.

Conjunctival Pediatric-Type Follicular Lymphoma.

Pediatric-type follicular lymphoma is an uncommon B-cell lymphoma that primarily involves the lymph nodes of the head and neck of children and young adults. Ocular involvement is rare, with only 5 well-documented cases in the literature, all occurring in the conjunctiva. The authors describe a 20-year-old African American man with enlarging bilateral medial conjunctival nodules. Excisional biopsy of the larger left conjunctival lesion, clinically presumed to be pyogenic granuloma, revealed pediatric-type follicular lymphoma composed of expansile follicles with germinal centers containing mitotically active blastoid cells, which coexpressed CD20, CD10, and BCL6 and lacked expression of BCL2. Polymerase chain reaction for immunoglobulin heavy chain rearrangement identified a monoclonal B-cell population. Fluorescence in situ hybridization studies failed to demonstrate BCL2, BCL6, and MALT1 gene rearrangements. Next-generation sequencing revealed a pathogenic MAP2K1 mutation, known to be enriched in pediatric-type follicular lymphoma. This report summarizes the clinical and pathologic diagnostic findings, biologic behavior, and management of conjunctival pediatric-type follicular lymphoma.

Femtosecond laser-assisted cataract surgery in complex cases.

PURPOSE: To describe the use of the femtosecond laser in complex cataract cases. SETTING: Department of Ophthalmology, University of Colorado, Aurora, Colorado, USA. DESIGN: Retrospective case series. METHODS: This was a single-center retrospective review of consecutive complex cataract surgery cases in which the Lensx femtosecond laser was used between October 2012 and February 2015. Complex cases were defined as white cataracts, dense brunescent cataracts, or cataracts in which zonulopathy was identified preoperatively. Outcome measures included an assessment of the capsulotomy, surgical complications, and postoperative corrected distance visual acuity (CDVA). RESULTS: Thirty-four eyes of 34 patients were included in this study; 27 had white cataract, 3 had dense brunescent cataract, and 6 had zonulopathy (2 of these also had white cataract). Three patients had an incomplete capsulotomy, and 3 had small radial tears in the anterior capsule. Four patients (11.7%) developed posterior capsule tears during phacoemulsification; 1 of these subsequently had pars plana vitrectomy for a retained lens fragment. Twenty-eight (97%) of 29 patients had a postoperative CDVA of 20/40 or better. Three patients were identified with comorbidities that limited postoperative CDVA. One patient developed postoperative cystoid macular edema. CONCLUSION: The femtosecond laser was useful in the surgical approach to patients with complex cataracts, especially for the creation of the capsulotomy. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Balloon cell nevi of the conjunctiva: Clinicopathologic correlation and literature review.

Balloon cell nevi are rare, benign melanocytic tumors that may involve the conjunctiva, choroid, and skin. In the ocular adnexa they typically present as raised and mobile hyperpigmented masses. Histologically, balloon cell nevi consist of large cells forming nests that usually lack melanin pigment. The balloon cells have a clear or vacuolated cytoplasm with centrally located nuclei. The vacuolated cytoplasm may be the result of defective melanin synthesis, with the accumulation of melanin precursors in premelanosomes. Balloon cells can resemble xanthoma cells, adipocytes, macrophages, sebaceous adenomas, melanoma with balloon cell changes, and metastatic renal cell carcinoma. Differentiating between these various entities via morphology and immunohistochemistry thus remains clinically significant. We report three cases of conjunctival balloon cell nevi and review the literature.

Scleral necrosis secondary to nonabsorbable suture following ptosis surgery.

We report a unique case of persistent scleral ulceration in a 68-year-old woman who developed eye redness, pain, and photophobia 2 days following external levator advancement with nonabsorbable suture. Slit-lamp biomicroscopy revealed an area of scleral ulceration superonasal to the limbus. The patient was treated with 6 months of topical steroids with some improvement in her condition but without complete resolution. An exposed suture or foreign body was never directly visualized; however, a mobile nodule was noted upon palpation of the eyelid. Subsequent surgical eyelid exploration revealed a retained polypropylene suture, which was dissected free and removed. Postoperatively, the area of scleral ulceration resolved completely.

Expression of α-crystallin in the retina of human sympathetic ophthalmia.

Sympathetic ophthalmia (SO) is a bilateral, granulomatous, intraocular inflammation that occurs following a penetrating injury to one eye, and has the potential to cause blindness of both eyes. The aim of this study was to examine the expression of α-crystallin and to detect apoptotic cells in the retina of human eyes with SO. Five globes, including three with SO and two age-matched normal appearing retinae, were examined. Formalin-fixed, paraffin-embedded tissue sections were submitted to hematoxylin and eosin staining and immuno-histochemistry with anti-αA and αB-crystallin antibodies. Apoptotic cells were detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) method, and double-staining immunohistochemistry was conducted together with the TUNEL reaction. In normal-appearing retina, αA-crystallin immunoreactivity was predominantly detected in the cytoplasm of photoreceptors, where αB-crystallin was less marked. In SO globes, granulomatous inflammation was noted in the choroid, whereas the retina and choriocapillaris were preserved. Immunoreactivity for αA-crystallin was detected in the retina, as well as in the cytoplasm and inner/outer photoreceptor segments. By contrast, αB-crystallin was weakly noted in the SO retina. Double-staining immuno-histochemistry revealed no TUNEL-positive photoreceptors in the retina displaying high immunoreactivity for αA-crystallin, but photoreceptor apoptosis was noted where expression of αA-crystallin was relatively low. The present study demonstrated that αA-crystallin was up-regulated in the cytoplasm of photoreceptors in the SO retina. This may play a protective role in the suppression of photoreceptor apoptosis associated with intraocular inflammation.

Outcomes of birdshot chorioretinopathy treated with an intravitreal sustained-release fluocinolone acetonide-containing device.

PURPOSE: To evaluate outcomes in birdshot chorioretinopathy following intravitreal implantation of a fluocinolone acetonide-containing drug delivery device. DESIGN: Retrospective, multicenter, interventional case study. METHODS: University- and community-based tertiary care. Twenty-two HLA-A29+ birdshot patients (36 eyes) were implanted with a sustained-release corticosteroid device and followed for up to 3 years. Main outcome measures were Snellen acuity, intraocular inflammation, adjunctive therapy, cataract, ocular hypertension, or glaucoma. Paired Wilcoxon statistics were used to analyze visual acuities; paired McNemar statistics were used to analyze presence or absence of other outcomes. RESULTS: Nineteen of 22 patients (32 eyes) completed 12 months of follow-up with improvement in median visual acuity (P=.015). Prior to implantation, 18 of 22 patients (82%) received immunosuppressive therapy versus 1 of 19 (5%) by 12 months (P<.001). Eyes with zero vitreous haze increased from 7 of 27 scored eyes (26%) at baseline to 30 of 30 eyes (100%) by 12 months (P<.001). Cystoid macular edema decreased from 13 of 36 eyes (36%) at baseline to 2 of 32 eyes (6%) at 12 months (P=.006). Five of 24 phakic eyes at baseline exited the study before surgery; all other eyes received cataract surgery. One hundred percent of study eyes had ocular hypertension, required intraocular pressure-lowering therapy, or had glaucoma surgery by 12 months. CONCLUSIONS: Implantation of a fluocinolone acetonide-containing intraocular device in birdshot chorioretinopathy can improve vision, control inflammation, and eliminate systemic therapy. There is a high incidence of cataract progression and intraocular hypertension or glaucoma.

Long-term follow-up of acute retinal necrosis.

PURPOSE: The purpose of this study was to report long-term visual outcome of acute retinal necrosis. METHODS: Medical records of patients with acute retinal necrosis were reviewed. RESULTS: Thirty-two patients were diagnosed with acute retinal necrosis from 1998 to 2007. Twenty patients (25 eyes) had at least 1 follow-up and available medical records. Intravitreal injections of ganciclovir and/or foscarnet were administered in 11 of 25 eyes. Intravenous and oral antiviral medications were used in 14 of 20 and 19 of 20 patients, respectively. Eleven of 25 eyes had <25% of retina affected, 8 of 25 had 25% to 50% of retina affected, and 6 of 25 had >50% of retina affected. Mean visual acuity at all time points was best when retinitis involved <25% and decreased as area increased. All but 1 eye with >50% involvement experienced decreased vision regardless of treatment. Three of 4 eyes with 25% to 50% involvement that received intravitreal antivirals had an improvement in visual acuity of > or =2 Snellen lines. Five of 25 eyes developed retinal detachment. None of the six eyes treated with prophylactic laser detached. CONCLUSION: Greater extent of retinitis portends a worse visual prognosis. Although intravitreal treatment did not prevent visual acuity loss in patients with severe disease, patients with moderate disease (25-50% retina involved) did well with intravitreal therapy with most having stable or improved visual acuity. Prophylactic laser decreased the rate of detachment.

Histopathologic and immunohistochemical studies of keratoglobus.

OBJECTIVE: To examine histopathologic and immunohistochemical features of human corneal buttons from patients who developed keratoglobus. METHODS: Nine corneal buttons were obtained during penetrating keratoplasty from patients with keratoglobus. Histologic features were examined using hematoxylin-eosin-stained sections. Immunohistochemical staining for alpha1-proteinase inhibitor, Sp1, and matrix metalloproteinases 1, 2, and 3 was performed, with 2 normal and 2 corneal sections with keratoconus as controls. RESULTS: Hematoxylin-eosin staining revealed diffuse stromal thinning and focal disruptions in Bowman's layer in all keratoglobus specimens. Similar abnormal immunostaining results for alpha1-proteinase inhibitor and Sp1 were detected in keratoglobus and keratoconus at their respective active disease sites. Immunostaining for matrix metalloproteinases 1, 2, and 3 was significantly more intense in corneas with keratoglobus than in normal controls. Matrix metalloproteinase staining intensity was especially prominent in areas where the underlying Bowman's layer was disrupted. CONCLUSIONS: Histological features in our keratoglobus specimens are consistent with previous reports. The similarities in immunohistochemical labeling between keratoglobus and keratoconus suggest that these entities may share common mechanisms that are involved in stromal thinning.

Keratectasia after laser in situ keratomileusis: a histopathologic and immunohistochemical study.

OBJECTIVE: To examine histopathologic and immunohistochemical features of human corneal buttons from patients who developed keratectasia after laser in situ keratomileusis (LASIK). METHODS: Five corneal buttons were obtained during penetrating keratoplasty from patients who developed keratectasia after LASIK. Histologic features were examined by hematoxylin-eosin staining using paraffin-embedded sections and by transmission electron microscopy. Immunostaining for alpha(1)-proteinase inhibitor, Sp1, and matrix metalloproteinases 1, 2, and 3 was performed with 2 healthy corneas and 2 corneas with keratoconus as controls. RESULTS: Central stromal thinning was observed after hematoxylin-eosin staining in all corneas with keratectasia. No histologic features specific to keratoconus, including Bowman layer disruption, were identified in the corneas with keratectasia. By transmission electron microscopy, collagen fibril thinning and decreased interfibril distance were observed in the stromal bed. Immunostaining intensity and/or pattern for alpha(1)-proteinase inhibitor and Sp1 in the corneas with keratectasia was comparable to that of healthy corneas and differed from that in the corneas with keratoconus. No significant staining with anti-matrix metalloproteinases 1, 2, and 3 antibodies was observed in either the corneas with keratectasia or the healthy corneas. CONCLUSIONS: Histologic findings suggest that post-LASIK keratectasia results in collagen fibril thinning and decreased interfibril distance within the residual stromal bed. Discrepant results between keratectasia and keratoconus suggest that the pathogenesis of the 2 conditions differ.

Human anterior chamber angle development without cell death or macrophage involvement.

PURPOSE: The iridocorneal angle in the mammalian eye including the trabecular meshwork (TM) develops from undifferentiated mesenchyme/neural crest between the iris root and cornea. The precise mechanisms underlying anterior angle development are unclear, and the contribution of cell death and phagocytic resorption by macrophages in angle development is controversial. In this study, we examined the human anterior chamber angle during various stages of development for evidence of cell death and phagocytic resorption. METHODS: Eyes from the human fetus (F) of 7, 8, 9, 10, 11, 13, 15, 18, 19, 21, 22, 23, and 27 weeks as well as eyes from 5- and 11-month-old children and donors 24, 48, and 67 years of age were obtained. Formalin-fixed and paraffin-embedded sections were examined by hematoxylin and eosin (H&E) staining. Immunohistochemistry was performed using polyclonal antibodies against CD68. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) labeling was also performed to evaluate cell death. RESULTS: By light microscopy, the development of human angle structures appeared to progress as previously described. Histological evidence of cellular death or resorption by macrophages was not observed. Furthermore, the chamber angle tissues did not stain with CD68 at any stage of development. Few CD68 positive cells were observed in the iris stroma and the anterior ciliary body between fetal weeks 10 and 18 (F10w and F18w). TUNEL labeled nuclei were not detected in the anterior chamber angle in any fetal or infant eyes. By contrast, TUNEL positive nuclei in TM cells were observed in the examined adult donor specimens. CONCLUSIONS: The results suggest that at the time points examined, neither cell death nor phagocytic resorption with macrophages appear to play a role in the development of the human anterior chamber angle.

Objective measurement of periocular pigmentation.

PURPOSE: To evaluate the Minolta CR-400 chromameter in objectively measuring periocular/facial pigmentation in subjects of different ethnicities. METHODS: The CR-400 was used to obtain skin color measurements from 75 African-American, Caucasian and Hispanic subjects in 16 facial and periocular locations. Comparisons between ethnic and Fitzpatrick groups and instrument reliability were analyzed. RESULTS: Significant differences in L* were observed among all three ethnic groups, while values a* and b* were less sensitive to differences in pigmentation. Comparison between Fitzpatrick groups again identified value L* as being the most sensitive, demonstrating significant differences between the more heavily pigmented groups. The 16 facial locations measured were found to be statistically similar to each other, and the chromameter demonstrated excellent inter- and intra-instrument reliability. CONCLUSIONS: The Minolta CR-400 chromameter reliably measures facial pigmentation and can be useful for studies evaluating changes in skin pigmentation. Value L* is the parameter that is most sensitive to differences between ethnic and Fitzpatrick groups. Overlap between groups was observed, demonstrating that in future studies, each individual must serve as their own control when monitoring changes in pigmentation. The similarity between all the locations tested demonstrates uniformity of facial pigmentation within an individual.